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Bladder Urothelial Carcinoma

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Bladder Urothelial Carcinoma. Core disease mechanisms, molecular and cellu...

2026-04-11
Asta MONDO:0005611 Model: Asta Scientific Corpus Retrieval 19 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Bladder Urothelial Carcinoma. Core disease mechanisms, molecular and cellu...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 19
  • Snippets retrieved: 20

Relevant Papers

[1] Involvement of Mitochondrial Dysfunction, Endoplasmic Reticulum Stress, and the PI3K/AKT/mTOR Pathway in Nobiletin-Induced Apoptosis of Human Bladder Cancer Cells

  • Authors: Y. Goan, Wen-Tung Wu, Chih-I Liu, C. Neoh, Yu-Jen Wu
  • Year: 2019
  • Venue: Molecules
  • URL: https://www.semanticscholar.org/paper/b7ffbf166cebef53a8d8e194da74bd5ce205619a
  • DOI: 10.3390/molecules24162881
  • PMID: 31398899
  • PMCID: 6719163
  • Citations: 50
  • Influential citations: 1
  • Summary: The results suggested that the cytotoxic and apoptotic effects of NOB on bladder cancer cells are associated with endoplasmic reticulum stress and mitochondrial dysfunction.
  • Evidence snippets:
  • Snippet 1 (score: 0.586) > Urothelial carcinoma of the transitional epithelium is also called transitional cell carcinoma (TCC), and can develop in the urothelium of the renal pelvis, ureter, or bladder. Urothelial carcinoma is the fifth most malignant tumor in the world, and the second most common cancer of the genitourinary tract [1,2]. Clinical evidence has demonstrated that urothelial carcinoma accounts for approximately 90-95% of all bladder cancers, and therefore more than 90% of human bladder tumors are TCCs [3,4]. TCC is an important disease in the aging population, especially as the proportion of women suffering from cancer increases with age [5]. The routes of TCC metastasis to nearby tissues include the local invasion of perivesical tissues and lymphatic spread to other sites [6]. The most common treatment for bladder TCC is surgical removal, followed by immunotherapy and chemotherapy. Bacillus Calmette-Guérin (BCG) is the most commonly-used agent for bladder perfusion therapy. When BCG is used in immunotherapy for the treatment of bladder cancer, it stimulates the host immune system, which is thought to be the mechanism by which the tumor is destroyed [7,8]. In recent years, radiation therapy and concurrent systemic chemotherapy have been proven to be effective in patients with bladder cancer for whom radical cystectomy is unsuitable [9,10]. However, every treatment method has its limitations, and the development of new diagnostic techniques and treatments for TCC remains an urgent issue. > Chemotherapy is a treatment in which certain drugs are employed to directly kill cancer cells or to stop them from growing and spreading, and its mechanism involves causing apoptosis. Chemotherapy is currently the most conducive to the development of new cancer treatments [11]. The two major apoptotic responses in mammalian cells are the intrinsic and extrinsic pathways, and signaling of the intrinsic pathway occurs in the mitochondria and endoplasmic reticulum (ER) [12,13].

[2] Genetic profiling and pathway analysis in bladder carcinoma: Implications for therapeutic targeting

  • Authors: Sampara Vasishta, U. Adiga, Alfred J Augustine
  • Year: 2025
  • Venue: Turkish Journal of Surgery
  • URL: https://www.semanticscholar.org/paper/405be9f362a5373a199f2dab695c9f0bf33d4e85
  • DOI: 10.47717/turkjsurg.2025.2025-3-33
  • PMID: 40726145
  • PMCID: 12687403
  • Summary: Comprehensive insights into the molecular underpinnings of bladder carcinoma are provided, highlighting interconnected pathways and potential therapeutic targets that could be exploited for therapeutic intervention.
  • Evidence snippets:
  • Snippet 1 (score: 0.575) > Objective Bladder carcinoma represents a significant challenge in oncology due to its heterogeneous molecular nature. This study aimed to identify key genetic factors and molecular pathways involved in bladder carcinoma pathogenesis to facilitate the development of targeted therapies. Material and Methods The top 30 genes associated with bladder carcinoma were retrieved from the disease gene network database. Comprehensive bioinformatic analysis was performed using various enrichment tools, including gene ontology biological process, cellular component, molecular function analyses, and pathway mapping through WikiPathways and metabolite associations through human metabolome database. Drug interactions were evaluated using DrugMatrix data. Results Gene ontology analysis revealed significant enrichment of cancer-related biological processes, cellular components, and molecular functions. Pathway analysis identified strong associations with head and neck squamous cell carcinoma, cancer pathways, pleural mesothelioma, endometrial cancer, and bladder cancer pathways. Key genes including CDKN2A, PTEN, EGFR, PIK3CA, HRAS, FGFR3, and TP53 were implicated across multiple pathways. Metabolite analysis showed significant associations with phosphatidylinositol derivatives, highlighting the importance of the PI3K pathway. Drug interaction analysis revealed potential modulatory effects of several compounds including sertraline, valproic acid, and hydroxyurea on gene expression patterns in bladder carcinoma. Conclusion This study provides comprehensive insights into the molecular underpinnings of bladder carcinoma, highlighting interconnected pathways and potential therapeutic targets. The significant overlap with other cancer types suggests common oncogenic mechanisms that could be exploited for therapeutic intervention. Further validation of these findings in clinical samples may facilitate the development of personalized treatment approaches for bladder carcinoma patients.
  • Snippet 2 (score: 0.570) > Integrated analyses of genomic, transcriptomic, and proteomic data have identified distinct molecular subtypes with different clinical behaviors and treatment responses (15). Furthermore, epigenetic alterations, including DNA methylation and histone modifications, have emerged as important regulators of gene expression in bladder cancer, adding another layer of complexity to the disease (16). > Understanding the intricate network of signaling pathways involved in bladder carcinogenesis is crucial for identifying potential therapeutic targets (17). Key pathways implicated in bladder cancer development include phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR, MAPK, WNT/β-catenin, and JAK/ STAT signaling, which regulate various cellular functions such as proliferation, survival, and invasion (18). Targeting these pathways represents a promising approach for developing novel therapeutic strategies with improved efficacy and reduced toxicity (19). > In this study, we aimed to comprehensively analyze the genetic and molecular landscape of bladder carcinoma by examining the top 30 genes associated with the disease from the disease gene network (DisGeNET) database (20). Through detailed pathway analysis, gene ontology (GO) enrichment, and exploration of metabolite and drug interactions, we sought to identify key molecular mechanisms and potential therapeutic targets for bladder carcinoma. Objectives 1. To identify and characterize the key genetic factors associated with bladder carcinoma through comprehensive bioinformatic analysis of DisGeNET data. 2. To elucidate the significant biological processes, cellular components, and molecular functions associated with bladder carcinoma-related genes using GO enrichment analysis. > 3. To map the molecular pathways implicated in bladder carcinoma pathogenesis and identify potential points of therapeutic intervention. 4. To explore associations between bladder carcinoma genes and metabolites, as well as drug interactions, to facilitate the development of targeted therapeutic approaches.

[3] Differentially expressed genes and interacting pathways in bladder cancer revealed by bioinformatic analysis

  • Authors: Yinzhou Shen, Xuelei Wang, Yongchao Jin, Jiasun Lu, Guangming Qiu et al.
  • Year: 2014
  • Venue: Molecular Medicine Reports
  • URL: https://www.semanticscholar.org/paper/6016208e207192d93586a9715252fed55df71013
  • DOI: 10.3892/mmr.2014.2396
  • PMID: 25050631
  • PMCID: 4148370
  • Citations: 8
  • Influential citations: 1
  • Summary: The results show that BCa involves dysfunctions in multiple systems and is expected to pave ways for immune and inflammatory research and provide molecular insights for cancer therapy.
  • Evidence snippets:
  • Snippet 1 (score: 0.563) > Bladder cancer (BCa) is a heterogeneous disease with a variable disease history. At present, BCa is the ninth most common tumor worldwide (1), ranking fourth among men and ninth among women (2). In the United States, ~10,400 new BCa cases emerge and 36,500 BCa-related deaths occur every year (3). The diseases of urothelial carcinoma can be classified depending on their depth of invasion as: pTa (papillary), pT1 (lamina propria invasion), pT2 (muscle invasion), pT3 (invasion to peri-vesical fat) and pT4 (locally advanced). > BCa has a multifactorial etiology. Numerous studies have identified risk factors for the development of BCa and the affected cellular processes, including low-penetrance gene polymorphisms, smoking (4), occupational exposure to aromatic amines and schistosomiasis infection (5,6). In addition, the fact that men are 3-4 times more frequently affected than women indicates hormone regulation as an additional factor (7,8). > The detection of BCa remains difficult due to the lack of specific tumor markers and the emergence of new symptoms. There is no standard therapy for patients with BCa; treatment options include surgery, chemo-, biological and radiation therapy. In addition, these methods show currently limited effectiveness, which is further reduced by the high recurrence of BCa and the high mortality deriving from increased rates of progression of the disease (9). There is thus an urgent need to develop more specific and efficient diagnostic tools and therapeutic approaches to better understand and treat the onset and course of BCa. > Earlier studies have suggested that different mechanisms have evolved to respond to specific phenotype alterations in the molecular and cellular pathways involved in BCa. A number of genetic variations in major carcinogenesis-related pathways can induce BCa. For example, in healthy cells, the cell cycle is controlled by tightly linking the p53 and retinoblastoma (RB) pathways that influence regulation of apoptosis, signal transduction and gene expression.

[4] Loss of p53 and Acquisition of Angiogenic MicroRNA Profile Are Insufficient to Facilitate Progression of Bladder Urothelial Carcinoma in Situ to Invasive Carcinoma*

  • Authors: Francisco Ayala de la Peña, K. Kanasaki, M. Kanasaki, N. Tangirala, G. Maeda et al.
  • Year: 2011
  • Venue: The Journal of Biological Chemistry
  • URL: https://www.semanticscholar.org/paper/11388c054d574510a553634e44062ded06519aac
  • DOI: 10.1074/jbc.M110.198069
  • PMID: 21388952
  • Citations: 68
  • Influential citations: 3
  • Summary: The results support the notion that activation of angiogenesis and loss of p53 are not sufficient for progression to invasive cancer and identify a new mouse model for bladder cancer that can be used to study factors that determine progression to an invasive phenotype of bladder cancer.
  • Evidence snippets:
  • Snippet 1 (score: 0.562) > Urothelial carcinomas of the bladder are among the most frequent human cancers and account for more than 14,000 deaths annually in the United States (1). Most cases of urothelial cancer are superficial bladder tumors, but around 20% of them are invasive carcinomas that can generate metastasis at the initial presentation or later in the evolution of the disease. Two groups of superficial bladder tumors have been described (2). Low grade papillary neoplasms are the most frequent, with a low potential of transformation into invasive cancer. Conversely, carcinomas in situ (CIS) 3 are biologically more aggressive and carry a high probability of turning into an invasive carcinoma. The molecular basis of urothelial bladder cancer is being progressively unveiled, and the generation of transgenic mouse models of bladder cancer obtained through the urothelial expression of oncogenes (SV40) (3) or deletion of tumor suppressor genes remains a viable strategy for unraveling this mechanism. It is acknowledged that there are at least two different pathways driving the malignant transformation of urothelium, each of them corresponding to one of the two types of urothelial tumors. The pathway leading to CIS, which is speculated to involve a loss of function of p53 (4), is particularly important due to its role as precursor of invasive disease. However, p53 deletion does not seem to be sufficient for urothelial tumorigenesis unless there is either a concurrent deletion of pRb (5,6) or Pten (7) or a concurrent H-ras activation (8). > Bladder urothelial carcinoma in situ poses a difficult conundrum in the clinical setting. Its high recurrence rate (90% of cases) and its frequent evolution to invasive disease make it a target for aggressive treatment regimens, such as bladder bacillus Calmette-Guerin therapy or cystectomy as in cases of extensive or persistent disease presentation (9). Angiogenesis is among the biological factors that have been studied as potential predictors of progression to invasive tumors in superficial bladder carcinoma and is considered by some groups as a useful biomarker (10). In this regard, some clinical studies have suggested that elevated microvessel density, an indicator of angiogenic

[5] Identification of key genes associated with bladder cancer using gene expression profiles

  • Authors: Yuping Han, Xuefei Jin, Hui Zhou, B. Liu
  • Year: 2017
  • Venue: Oncology Letters
  • URL: https://www.semanticscholar.org/paper/f21f6e9bf314ae76745a3c773a4498e57f4c2170
  • DOI: 10.3892/ol.2017.7310
  • PMID: 29375713
  • PMCID: 5766060
  • Citations: 17
  • Summary: The DEGs associated with the cell cycle may serve pivotal roles in the pathogenesis of bladder cancer, as identified in functional and pathway enrichment analyses.
  • Evidence snippets:
  • Snippet 1 (score: 0.560) > Bladder cancer is one of the most common types of cancer worldwide and was the most common urological tumor in China in 2012 (1). In 2012, of the individuals with bladder cancer, 90% were diagnosed at >65 years-of-age worldwide (2). This disease is a common malignancy characterized by a poor clinical outcome (3); therefore, investigations into the underlying molecular mechanisms are urgently required in order to facilitate improvements in early diagnosis and treatments. > Bladder cancer is considered a genetic disease and is driven by the multistep accumulation of genetic and epigenetic factors that usually result in uncontrolled cellular proliferation, cell cycle deregulation or a decrease in cell death (3). The two different types of genetic alterations that are observed in bladder cancer are tumor protein p53 mutations and a number of single-nucleotide and structural variants, as well as chromosome shattering (4). Di Pierro et al (1) revealed that mutations in FGFR3 and TP53 are usually predictive of bladder malignancy. Overexpression of PIN2/TRF1-interacting telomerase inhibitor 1 in urothelial carcinoma of the bladder inhibited cell proliferation by inhibiting telomerase activity and the p16/cyclin D1 signaling pathway (5). Furthermore, chromosomal instability (CIN) characterized by loss or gain of chromosomal fragments or entire chromosomes is most prevalent in invasive urothelial cancer, compared with other less malignant papillary subtypes (6). Checkpoint dysfunction serves an important role in the development of CIN and is caused by defects in cell cycle regulation, p53 function and checkpoint signaling (7). Although certain studies have reported that gene mutations, telomerase activity and chromosomal instability are connected with bladder cancer (4-7), the exact molecular mechanism of bladder cancer remains unclear. A profound understanding of the molecular mechanism of action may be useful to provide an improved, more efficient handling of bladder cancer. > In the present study, the raw microarray data GSE52519 were downloaded to investigate the underlying molecular mechanisms of bladder cancer.

[6] Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder

  • Authors: Shinsuke Oda, M. Fujisawa, Chunning Li, Toshihiro Ito, Takahiro Yamaguchi et al.
  • Year: 2021
  • Venue: PLoS ONE
  • URL: https://www.semanticscholar.org/paper/ed2feab35efacb7fff24568d8720f50601342738
  • DOI: 10.1101/2021.07.23.453537
  • PMID: 34818323
  • PMCID: 8612556
  • Citations: 7
  • Summary: Aberrant activation of the Ras/Raf/ERK (extracellular-signal-regulated kinase)-MAPK (mitogen-activated protein kinase) pathway is involved in the progression of cancer, including urothelial carcinoma; but the negative regulation remains unclear. In the present study, we investigated pathological expression of Spred2 (Sprouty-related EVH1 domain-containing protein 2), a negative regulator of the Ras/Raf/ERK-MAPK pathway, and the relation to ERK activation and Ki67 index in various categories o...
  • Evidence snippets:
  • Snippet 1 (score: 0.552) > Bladder cancer is a highly prevalent disease and its incidence is steadily rising worldwide [1]. In the United States, bladder cancer is the 4th most incident and 8th most deadly tumor among men [2]. Most of the bladder cancer is urothelial carcinoma arising from urothelial epithelium. Evidence indicates that urothelial carcinoma has two distinct clinical subtypes with distinct molecular features at bladder tumor initiation; low-grade tumors (superficial papillary) and high-grade tumors (flat, represented by carcinoma in situ) [3,4]. Low-grade tumors, i.e., papillary urothelial neoplasm of low malignant potential or low-grade papillary urothelial carcinoma, do not easily progress to high-grade papillary urothelial carcinoma or invasive carcinoma [5,6]. Recently, a comprehensive landscape of molecular alterations in urothelial carcinomas was shown [7]. More than 70% of low-grade papillary carcinomas harbor FGFR3 gene mutation [8]. On the other hand, flat carcinoma in situ (CIS) often develops to invasive urothelial carcinoma [9,10], in which allelic deletion of the TP53 (p53) and PTEN (tumor-suppressor) [11] and retinoblastoma gene (RB, negative cell cycle regulator) [12] is common. > In addition to the gain of function gene mutations, extracellular-regulated kinase (ERK) plays a crucial role in cancer development and progression [13,14]. The Ras/Raf/ERK-MAPK (mitogen-activated protein kinase) pathway, one of the serine/threonine kinases of MAPKs pathway, is a major determinant to promote cell proliferation, differentiation, and survival, and plays an important role in bladder cancer prognosis [15]. ERK activation was observed in high-grade non-invasive and invasive urothelial carcinoma [16], suggesting that robust ERK activation contributes to urothelial tumorigenesis with a high malignant potential. > Signaling pathways are counterbalanced by endogenous inhibitory mechanism(s).

[7] Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges.

  • Authors: M. Garg
  • Year: 2016
  • Venue: World journal of stem cells
  • URL: https://www.semanticscholar.org/paper/ddabb19e5a1d0e073b6130fbba36269c066d294a
  • DOI: 10.4252/wjsc.v8.i8.260
  • PMID: 27621760
  • Citations: 18
  • Influential citations: 1
  • Summary: Transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition and discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance.
  • Evidence snippets:
  • Snippet 1 (score: 0.518) > Urothelial carcinoma (UC) of the bladder, also known as transitional cell carcinoma of the bladder, is the sixth most common cause of cancer-related deaths worldwide [1] . It is the second most frequent cancer of the genitourinary tract where men are at four times greater risk than women. It is caused by the accumulation of genetic or epigenetic changes in the urothelium due to its exposure to multiple risk factors including tobacco and occupational/environmental carcinogens (polycyclic aromatic hydrocarbons). People working in leather, dye, rubber industries, painters, pesticide applicators or those having chronic urinary tract infections are more prone to develop urothelial carcinoma. > UC of the bladder is a heterogeneous disease, which can arise through two different pathways -non-invasive papillary pathway and invasive pathway. It represents a spectrum of neoplasms, including non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and metastatic lesions. Tumor staging and grading (Tumor Node and Metastasis classification by World Health Organization/International Society of Urology Pathologists, 2004) are the gold standard prognosticators for defining the various entities of UC of the bladder (Figure 1) [2] . Despite the successful treatment of NMIBC through transurethral resection of bladder tumor (TURBT), 70% to 80% of them have a tendency to recur. Hence, there is a need for regular cystoscopy and examination of cytologic and molecular markers in urine, blood or tumor tissues in bladder cancer patients. This intense surveillance after treatment makes this cancer, one of the most costliest cancers to manage. Although in the majority of the cases, these papillary bladder tumors are not lethal, however, 20%-30% of them can progress to more aggressive, invasive and metastatic bladder tumors with an overall survival rate of 5% (Figure 2). > Characterization of molecular and biological mechanisms responsible for distinct bladder tumor phenotypes would facilitate personalization of more effective treatment decisions. Multiple genetic and epigenetic abnormalities are known to be associated with diverse types of urological malignancies.

[8] Differential Expression of One‐Carbon Pathway Enzyme ALDH1L1 Is Linked to Tumorigenicity of Low‐Grade Bladder Cancer Cells Through Metabolic Reprogramming

  • Authors: H. Meyers, Jaspreet Sharma, Amira A. Abdellatef, Mikyoung You, David Raines et al.
  • Year: 2025
  • Venue: Cancer Medicine
  • URL: https://www.semanticscholar.org/paper/ea661c7a0e1e815ed14f5660ad7a7215577dcf6c
  • DOI: 10.1002/cam4.71291
  • PMID: 41070972
  • PMCID: 12512356
  • Summary: This work investigated how differential ALDH1L1 expression affects cellular characteristics and tumorigenicity of RT4 cells as well as tumor metabotypes.
  • Evidence snippets:
  • Snippet 1 (score: 0.517) > Bladder cancer, a common malignancy that typically affects older adults, is a global health concern leading to more than 220,000 deaths each year worldwide [1]. Major risk factors for bladder cancer include tobacco use, exposure to occupational carcinogens, chronic inflammation of the bladder, and genetic susceptibility [2]. Urothelial carcinoma is the most prevalent histological subtype of bladder cancer [1,3]. It is characterized by abnormal cell growth in the bladder's urothelial lining and exhibits a broad spectrum of clinical and pathological features, ranging from nonmuscle-invasive tumors to aggressive muscle-invasive types with a strong tendency to metastasize [4]. Although low-grade urothelial carcinoma has a lower risk of progressing to invasive disease, its high recurrence rate and requirement for continuous monitoring pose a significant clinical challenge and contribute considerably to a healthcare burden [5]. > At the molecular level, bladder cancer is marked by genetic alterations and dysregulation in key signaling pathways that drive uncontrolled cell proliferation, survival, and invasion [6]. These include mutations in the fibroblast growth factor receptor-3 (FGFR-3) [7], chromosome 9 deletions [8], oncogenic HRAS [9], and dysregulation of the phosphatidylinositol 3-kinase (PI3K)/ AKT signaling [10,11]. Further, metabolic reprogramming, which provides the energy and biosynthetic precursors necessary for cancer progression, is increasingly recognized as a hallmark of bladder cancer [12]. Dysregulation in key metabolic pathways such as glycolysis and the TCA cycle, as well as altered lipid metabolism, are prominent features in bladder cancer cells [13]. Such metabolic reprogramming facilitates malignant processes in response to the exposure to environmental carcinogens by promoting the rapid proliferation and invasiveness of tumor cells. The importance of specific metabolic pathways in bladder cancer tumorigenesis and progression underscores the need for a deeper understanding of the role of key metabolic enzymes that regulate these pathways [12]. This knowledge is critical for bladder cancer prevention and the identification of suitable therapeutic targets for treating this cancer.

[9] Significance and Mechanisms Analyses of RB1 Mutation in Bladder Cancer Disease Progression and Drug Selection by Bioinformatics Analysis

  • Authors: Dingguo Zhang, Jinjun Tian, Qier Xia, Zhenyu Yang, B. Gu
  • Year: 2021
  • Venue: Bladder Cancer
  • URL: https://www.semanticscholar.org/paper/6038af24d56f6d9c5eeb1572c64dd5acd6aa62f2
  • DOI: 10.3233/BLC-200368
  • PMID: 38994537
  • PMCID: 11181786
  • Citations: 7
  • Summary: The significance of RB1 mutation in disease progression and drug selection in bladder cancer was suggested by the results, and multiple genes and pathways related to such a program were identified.
  • Evidence snippets:
  • Snippet 1 (score: 0.510) > Early and comprehensive intervention might be important for such patients to live longer. > Nowadays, molecular pathological diagnosis and individualized medicine testing can help doctors select target drugs according to the characteristics of the patient's tumor cells, including bladder cancer. Different patients may have tumor cells with different pathways activated in their bodies, which results in different molecular and pathological characteristics. These are the main mechanisms for disease progression and drug resistance in many tumors, which is also the basis of individualized treatment. Analyzing the activation of different pathways can help us understand the characteristics of different subtypes of tumors, and might help us explore potential personalized treatment at the same time. If a certain pathway is specifically activated in certain subtype patients, the drugs targeted this pathway might be more effective in such patients. Through these analyses, we can find out the potential mechanisms of drug resistance and clinical phenotypes that are associated with RB1 mutation, and provide some theoretical basis and directions for further research and verification. This might be quite preliminary and only have some theoretical functions. To explore these issues deeply, the gene expression data was analyzed in depth to find the key pathways and core genes associated with RB1 mutation. Results of GSEA analysis suggested that RB1 mutation were mainly associated with DNA repair, multiple cancer related pathways, cell proliferation and division, and metabolism. Previous researches have shown that defects in DNA repair contributed the disease progression of bladder cancer and influenced the treatment, especially in MIBC. Genomic alterations in the DNA repairassociated genes could render tumors sensitive to cisplatin-based chemotherapy for MIBC [20]. RB1 regulates the cell cycle. In RB1 mutated tumors, our findings showed that many processes involved in cell proliferation were enriched. RB1 mutation could result in abnormal regulation of cell cycle and cell division proliferation, which lead to continuous cell growth and tumor progression. Therefore, besides the three drugs above, other drugs, such as Docetaxel (Taxotere) which effectively induces G2M arrest and apoptosis might be more sensitive in patients with RB1 mutation [21]. > Next, we searched for DEGs and performed functional enrichment analysis on them. The results show a total of 999 DEGs. Enrichment analysis suggested that DEGs in RB1 mutated bladder cancer patients implicated with multiple cellular programs.

[10] A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes

  • Authors: Liang Wang, Bryan A Smith, N. Balanis, Brandon L. Tsai, Kim Nguyen et al.
  • Year: 2019
  • Venue: Proceedings of the National Academy of Sciences of the United States of America
  • URL: https://www.semanticscholar.org/paper/524e8cfd0183fb1f1800969a87b6a7ad05f7d45e
  • DOI: 10.1073/pnas.1915770117
  • PMID: 31871155
  • PMCID: 6955337
  • Citations: 32
  • Summary: A tumor model is provided as functional evidence showing that SCCB and other bladder cancer phenotypes can be derived from normal human urothelial cells and provides a transcriptional dataset and a preclinical model for further investigating S CCB biology.
  • Evidence snippets:
  • Snippet 1 (score: 0.507) > Small cell carcinoma of the bladder (SCCB) is a lethal variant of bladder cancer with no effective treatment. A lack of available preclinical models and clinical cohorts impedes our understanding of its molecular pathogenesis. In this study, we provided a tumor model as functional evidence showing that SCCB and other bladder cancer phenotypes can be derived from normal human urothelial cells. We further demonstrated that SCCB has a distinct transcriptome and identified SCCB-associated cell surface proteins (CSPs) that can be further evaluated as potential therapeutic targets. We show that our model shares CSP profile with clinical SCCB samples. Our findings create a foundation to understand the molecular underpinnings of SCCB and provide tools for developing therapeutic strategies. > Bladder cancer histological phenotypes have diverse clinical manifestations. The 5-y survival rate for in situ urothelial carcinoma is 95.7% and is 35.2% when tumors spread to regional lymph node (8), whereas for SCCB it is only 21.8% (9). In clinical samples, SCCB is found frequently in combination with other bladder cancer phenotypes (10). A recent genetic study comparing genetic alterations in small-cell lung cancer and SCCB suggests that SCCB originates from urothelial cells (11). However, the mechanisms underlying its development are largely unknown. Bladder cancer subtypes defined by gene-expression profiles are associated with different histological features, treatment responses, and distinct patient outcomes (12)(13)(14). Understanding the pathogenesis and molecular differences between SCCB and other bladder cancer histological phenotypes may serve an entry point for studying their diverse clinical consequences. > A lack of tumor models and patient samples limits our ability to study the pathogenesis and molecular features of SCCB. SCCB tumors can be generated using patient-derived xenograft models (7). However, the establishment of a patient-derived xenograft model relies on clinical SCCB samples and thus cannot provide enough biological replicates partly due to the rarity of SCCB cases (15). Genetically engineering noncancerous cells into subtypespecific tumors is an alternative strategy to establish tumor models (16). A recent study successfully initiated small cell carcino

[11] TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6

  • Authors: Sheng Luo, Wenjin Wang, Jingfang Feng, Rui Li
  • Year: 2021
  • Venue: Journal of Immunology Research
  • URL: https://www.semanticscholar.org/paper/ae32bf0f300b164790c8f1b0e3254640ad4641c6
  • DOI: 10.1155/2021/5975893
  • PMID: 34966825
  • PMCID: 8712183
  • Citations: 13
  • Summary: This work revealed that TEX10 could exert a significant carcinogenic effect on urinary bladder carcinoma tumorigenesis and radiotherapy resistance through the activation of XRCC6-related channels and offered a novel and feasible therapeutically related strategy for inhibiting urinary bladder cancer tumorigenicity.
  • Evidence snippets:
  • Snippet 1 (score: 0.506) > Bladder carcinoma ranked the tenth most frequent carcinoma worldwide has clinical manifestations and heterogeneous natural history [1]. Urothelial bladder carcinoma, featuring great recurrence rate, progression, and primary and acquired resistance to platinum-based therapy [2,3], refers to the main histological subtype of bladder carcinoma, which brings considerable economic burden to the health care system, and has a significant impact on the quality of life and overall prognosis of patients [1]. With the aging of the population, the incidence rate of bladder carcinoma is on the rise [4,5]. Current treatments for bladder carcinoma include a combination of surgery, targeted therapy, radiotherapy, and immunotherapy [6,7]. Bladder cancer is considered a chromatin disease due to the abnormally high mutation rate of chromatin proteins, pointing to the impor-tance of studying epigenetic disorders and the regulation prospects of this carcinoma [8][9][10][11][12][13]. At the molecular level, bladder carcinoma can be divided into six subtypes: papillary, unstable, nonspecific, squamous, neuroendocrine, and interstitial rich [14]. These subtypes have different patient outcomes, cell phenotypes, molecular characteristics, and genetic changes [14]. However, differences in treatment outcomes among patients with bladder carcinoma remain important clinical challenge [15][16][17]. Further in-depth research of the molecular mechanism is likely to help develop feasible therapeutically related strategies for bladder carcinoma. > TEX10, pertaining to the five friends of methylated chtop (chromatin-associated protein) as well as rix complexes, is critical to cell cycle regulation, ribosome biogenesis, and transcriptional regulation [18,19]. Most importantly, TEX10 is a new stemness factor, which interacts with Sox2, thus involving in the establishment and maintenance of pluripotency [20]. Tex10 has an enrichment under the place of superenhancers (SEs) based on a manner relying on Sox2, while coordinating DNA demethylation and histone ace

[12] CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration

  • Authors: Y. Gong, W. Qiu, X. Ning, Xinyu Yang, Li-bo Liu et al.
  • Year: 2015
  • Venue: Oncotarget
  • URL: https://www.semanticscholar.org/paper/28a99a42e51f18327685ca797f20e9d08d2f6a17
  • DOI: 10.18632/oncotarget.4624
  • PMID: 26312564
  • PMCID: 4694871
  • Citations: 46
  • Influential citations: 4
  • Summary: The findings revealed for the first time a potential oncogenic role for CCDC34 in bladder carcinoma pathogenesis and it may serve as a biomarker or even a therapeutic target for bladder cancer.
  • Evidence snippets:
  • Snippet 1 (score: 0.502) > Urothelial carcinoma of the bladder is a major cause of morbidity and mortality worldwide, with 180, 500 estimated new cases each year and 38, 200 deaths in the European Union [1], and with 74,000 estimated new cases and 16,000 deaths in United States [2]. Although localized bladder carcinomas could be managed by surgical resection, the recurrence and progression rates are still high. The therapeutic outcomes for patients with advanced bladder carcinoma who receive radiotherapy or chemotherapy remain unsatisfactory. The absence of more effective therapies for bladder carcinoma requires more research into the underlying molecular mechanisms of its tumorigenesis and the development of new treatment aimed at specific molecular targets. > Mitogen-activated protein kinase (MAPK) cascades are key signaling pathways involved in multiple biologic processes, such as cell proliferation, differentiation, death, migration, invasion and inflammation. Activation of MAPK is a frequent event in tumor progression and metastasis. Several components of the MAPK network have already been proposed as targets in cancer therapies, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Over-activation of Ha-ras occurred in human urothelial tumors and hyper-activation of the ras signaling pathway was responsible for the low-grade, non-invasive papillary bladder tumors [3]. The p38 MAPK was activated during the log phase growth of bladder cancer cells and regulated invasion of bladder cancer by modulation of MMP-2 and MMP-9 expression and activity [4]. Besides, PI3K/AKT/ mTOR is also a major intracellular signaling pathway, www.impactjournals.com/oncotarget which is frequently activated in diverse cancers and plays a very significant role in cell growth, tumorigenesis, cell invasion and drug response. Elevated levels of active Akt have been proposed to mediate resistance to the pro-apoptotic cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in bladder cancer cells and were reversible upon PI3K inhibition [5].

[13] Association between elevated PRIM1 expression and poor prognosis in human urothelial carcinoma

  • Authors: Ban A. Al-Hassany, I. M. Al-sudani
  • Year: 2026
  • Venue: Journal of Taibah University Medical Sciences
  • URL: https://www.semanticscholar.org/paper/7b3b6d69ccdb5d98a2e8853c757ee512070037ff
  • DOI: 10.1016/j.jtumed.2025.12.007
  • PMID: 41550244
  • PMCID: 12809060
  • Summary: Significant upregulation of PRIM1 expression was found to be associated with mutations in Retinoblastoma 1 (RB1), Ankyrin Repeat Domain 30A, Filamin A (FLNA), and Tectonin Beta-Propeller Repeat Containing 2 (TECPR2) in bladder cancer, highlighting the crosstalk between DNA replication machinery and genetic mutations in bladder cancer.
  • Evidence snippets:
  • Snippet 1 (score: 0.494) > Our findings suggested that PRIM1 might be a promising molecular biomarker in bladder urothelial carcinoma. Higher PRIM1 expression was strongly associated with lower overall survival rates in patients with bladder cancer (p < 0.05). This research also identified statistically significant associations between substantial PRIM1 overexpression and mutations in the tumor suppressor RB1, transcription factor ANKRD30A, cytoskeletal regulator FLNA, and autophagy-associated gene TECPR2. If PRIM1 mutations activate specific pathways affecting gene expression (e.g., ANKRD30A and FLNA), targeted drugs might potentially be used, such as inhibitors of proteins involved in the affected pathways, or drugs that block cellular proliferation or mutation-induced pathways. If mutations alter expression in ways that increase cancer cell activity or immune resistance, drugs such as PD-1 or PD-L1 inhibitors might be effective. Traditional chemotherapy is often used for patients with mutations that result in resistance to targeted therapies. In gene therapy, techniques such as CRISPR-Cas9 could be explored to edit or suppress PRIM1 and mitigate the mutation's effects. Clinical trials testing novel drugs targeting PRIM1 mutations or related pathways are a promising avenue. Our results revealed important mechanisms of bladder cancer molecular pathogenesis and might potentially guide the development of targeted therapies. In addition, PRIM1 might serve as a potential therapeutic target for urothelial carcinoma.

[14] Omega-3 Fatty Acids Inhibit Tumor Growth in a Rat Model of Bladder Cancer

  • Authors: B. Parada, F. Reis, Raquel Cerejo, P. Garrido, J. Sereno et al.
  • Year: 2013
  • Venue: BioMed Research International
  • URL: https://www.semanticscholar.org/paper/7dc228e89e302b2fd4906412e1d68f2a25701b77
  • DOI: 10.1155/2013/368178
  • PMID: 23865049
  • PMCID: 3705844
  • Citations: 30
  • Influential citations: 1
  • Summary: In conclusion, omega-3 fatty acids inhibit the development of premalignant and malignant lesions in a rat model of bladder cancer, which might be due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties.
  • Evidence snippets:
  • Snippet 1 (score: 0.490) > Bladder cancer, the fourth most common tumor in men and the eighth in women, remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression [1][2][3][4]. Mortality rates in muscle-invasive disease are still very high, despite the growing efforts on earlier diagnosis and aggressive and multidisciplinary treatments [4,5]. > In this context, preventive strategies are crucial for the management of bladder cancer, but they still demand a better elucidation of the carcinogenetic process. Exogenous factors, such as cigarette smoking, which accounts for a huge percentage of cases, as well as occupational carcinogens, such as aromatic amines and polycyclic aromatic hydrocarbons, are important determinants of the disease appearance [6,7]. > However, apart from the genetic features already characterized [8,9], the cellular and molecular mechanisms might involve inflammatory, proliferative, and oxidative stress phenomena that deserve further elucidation. In fact, the identification of promising drugs depends on continuous research concerning the molecular/cellular mechanisms underlying cancer appearance and progression. > The experimental model of rat bladder cancer induced by -butyl--(4-hydroxybutyl) nitrosamine (BBN) is an appropriate and validated model to study human cancer development. In fact, due to the histological similarities with the human bladder cancer, it has been the most used model for the study of tumor pathophysiology, as well as for the evaluation the efficacy of therapeutic strategies [10][11][12]. The urothelial carcinogenesis is a continuous and slow process that goes through molecular and morphological changes, BioMed Research International from benign to aggressive lesions, including initial dysplastic and proliferative epithelial abnormalities, preneoplastic changes, and malignant lesions (papilloma and carcinoma) [12][13][14]. Thus, an early treatment targeting these pathways could hypothetically prevent bladder cancer development and growth.

[15] British Association for Cancer Research/Association of Cancer Physicians/Royal Society of Medicine (Oncology Section) Joint Winter Meeting

  • Authors: R. Halaban, Y. Funasaka, J. Cowan, D Birnbaum, France et al.
  • Year: 1991
  • Venue: British Journal of Cancer
  • URL: https://www.semanticscholar.org/paper/8aa14ed0d9edb0d3032155050dbbc3881a186176
  • DOI: 10.1038/bjc.1991.185
  • PMCID: 1972403
  • Summary: Regulatory factors in normal and malignant melanocytes R. Halaban', Y. Funasaka, J. Cowan, & D. Birnbaum.
  • Evidence snippets:
  • Snippet 1 (score: 0.489) > Department of Histopathology, Royal Marsden Hospital, Fulham Road, London SW36JJ, UK. > Transitional cell carcinomas account for about 95% of bladder carcinomas in the UK. They are separable into subtypes with different behaviour and management: carcinoma in situ (CIS), superficial disease and muscle-invasive carcinoma. A principal prognostic factor is T stage, for which the preferred staging system remains the the-UICC 3rd Edition (1978) rather than the 4th Edition (1987). The so-called muscularis mucosae may form a prognostic subdividing line within TI tumours. For superficial tumours, factors reported as predis- posing to recurrence or progression include number and size of tumours, grade, coexistent CIS, cell surface blood group antigen status, aneuploidy, EGF receptor expression, and findings at 3 month follow up cystoscopy. Behaviour of muscle-invasive tumours may be influenced by tumour size, grade, pattern of invasion, lymphatic invasion and lymph nodal status. The presence of squamous metaplasia may affect response to radiotherapy. For other types of bladder carcinoma the prognosis is related principally to stage at presentation (squamous cell or adenocarcinoma), or to histo- logical subtype (small cell). > Molecular biology of bladder cancer M.A. Knowles, J.P. Cairns, L.M. Coombs & A.J. Proctor Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 OTL, UK. > A number of genetic changes are required for epithelial transformation. For several tumour types including colon, breast and lung, the identity of certain of the genes involved is now known, some of the molecular mechanisms involved in the generation of the transformed phenotype have been elucidated and clinical correlates with these molecular changes have been identified. Some changes are shared by several tumour types whilst others appear to be cell type specific. Recently, a number of frequent molecular alterations have been identified in transitional cell tumours.

[16] Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

  • Authors: Chuan Zhang, Mandy Berndt-Paetz, J. Neuhaus
  • Year: 2020
  • Venue: Diagnostics
  • URL: https://www.semanticscholar.org/paper/fa602f5c906dc97b5116f596eac58915454a2e48
  • DOI: 10.3390/diagnostics10020066
  • PMID: 31991631
  • PMCID: 7168923
  • Citations: 29
  • Influential citations: 2
  • Summary: The present study highlights an up to now unrecognized possible role of CASQ2 in cancer (BCa), and suggests that CRYAB may also be a candidate biomarker in BCa.
  • Evidence snippets:
  • Snippet 1 (score: 0.486) > Bladder cancer (BCa) is one of the most common malignancies, with a high rate of recurrence, and involves associated high morbidity and mortality, especially in advanced BCa [1]. Surgical resection, neoadjuvant chemotherapy, intravesical treatment, radiotherapy, and photodynamic therapy (PDT) are conventional therapeutic approaches to BCa [2][3][4]. According to the clinical spectrum of BCa, it is significant to explore the disease mechanisms, and to identify precise and effective biomarkers for early diagnosis of BCa with no significant clinical symptoms, for evaluating prognosis, and for developing effective strategies of BCa treatment. > Bladder cancer is mostly induced by exposure to toxic substances, and smoking is the leading risk factor. A papillary and a nonpapillary form of BCa are distinguished. Based on the heritage from different progenitor cells, those two forms lead to various molecular subtypes, with different clinical behavior. The superficial, luminal papillary tumors are genetically stable, remain noninvasive and nonmetastatic, and can be treated curatively by repeated transurethral resection. The invasive form derives from a different urothelial precursor, progresses to invasion of the bladder wall and metastasis [5]. Evidence of different basic molecular mechanisms comes from mouse models. Mutant ras genes induced urothelial hyperplasia at low copy numbers and papillary tumors at high copy numbers, while inactivation of the tumor protein p53 and retinoblastoma (RB1) pathways seem to induce carcinoma in situ (CIS) tumors, able to progress into invasive BCa [6,7]. Ras activation is coupled to the Wnt signaling β-catenin pathway, driving bladder tumorigenesis [8]. P53 alterations are involved in tumor progression to more aggressive forms [9] and the RB1 pathway plays a critical role in the regulation of the cell cycle and cell death [10,11]. Until now, there has been no consensus about the use of urinary markers or tests for non-muscle-invasive bladder cancer (NMIBC) from the international panels on bladder cancer [12][13][14].

[17] 3-BrPA eliminates human bladder cancer cells with highly oncogenic signatures via engagement of specific death programs and perturbation of multiple signaling and metabolic determinants

  • Authors: Eumorphia G. Konstantakou, G. Voutsinas, Athanassios D. Velentzas, Aggeliki-Stefania Basogianni, E. Paronis et al.
  • Year: 2015
  • Venue: Molecular Cancer
  • URL: https://www.semanticscholar.org/paper/16b70e29433b35c313fb8699564388fd02de165e
  • DOI: 10.1186/s12943-015-0399-9
  • PMID: 26198749
  • PMCID: 4511243
  • Citations: 40
  • Summary: 3-BrPA, a halogenated derivative of pyruvate and historically considered inhibitor of glycolysis, is employed to eliminate bladder cancer cells with highly oncogenic molecular signatures to represent a promising agent for bladder cancer targeted therapy.
  • Evidence snippets:
  • Snippet 1 (score: 0.484) > Urothelium lines the inner surfaces of almost the entire urinary track, including bladder. Urothelial carcinoma of the bladder is a major cause of mortality worldwide and it ranks fifth among all cancers in the Western world, with an estimated 150,000 deaths per year [1,2]. Bladder cancer is classified as either a low-grade, non-muscleinvasive disease, or a high-grade, muscle-invasive disease, which is likely to metastasize [1,3]. The main genetic alterations underlying low-grade papillary tumor development involve FGFR3, H-Ras and mTOR pathway member genes, whereas progression to high-grade invasive urothelial carcinoma depends on p53 and Rb tumor-suppressor networks [1,3]. However, an integrated study of 131 invasive bladder carcinomas revealed dysregulation of PI3K/ Akt/mTOR and RTK/Ras/MAPK pathways in 42 % and 44 % of the tumors, respectively [2]. Interestingly, distinct basal ("mesenchymal"-like) and luminal ("epithelial"-like) subtypes of muscle-invasive bladder cancer, with different sensitivities to frontline chemotherapy, have been recently identified [4,5]. Treatment of the disease has not advanced, in the past 30 years, beyond surgery and cisplatinbased combination chemotherapy, which is only effective in ~40 % of cases [2,4,6]. Therefore, novel strategies that target specific pathways in the malignant cell must successfully evolve and promptly pass the proof-of-principle tests in preclinical models and clinical trials [1,3,6]. > Reprogramming of energy metabolism has recently emerged as a new hallmark of cancer [7]. The best characterized metabolic phenotype of tumor cells is the Warburg effect, which is a shift from ATP generation through mitochondrial oxidative phosphorylation to ATP generation through glycolysis, even under normal oxygen concentrations [8,9]. Aerobic glycolysis seems to play an important role in supporting the large-scale biosynthetic programs that are required for active cell proliferation.

[18] CSTP1, a Novel Protein Phosphatase, Blocks Cell Cycle, Promotes Cell Apoptosis, and Suppresses Tumor Growth of Bladder Cancer by Directly Dephosphorylating Akt at Ser473 Site

  • Authors: D. Zhuo, Xiao-wei Zhang, Bo Jin, Zheng Zhang, Bu-shan Xie et al.
  • Year: 2013
  • Venue: PLoS ONE
  • URL: https://www.semanticscholar.org/paper/50f56e6437129b5519d290bc1fe65973cfcb8346
  • DOI: 10.1371/journal.pone.0065679
  • PMID: 23799035
  • PMCID: 3684612
  • Citations: 33
  • Influential citations: 5
  • Summary: A novel protein phosphatase CSTP1(complete s transactivated protein 1), which interacts and dephosphorylates Akt specifically at Ser473 site in vivo and in vitro, blocks cell cycle progression and promotes cell apoptosis is identified.
  • Evidence snippets:
  • Snippet 1 (score: 0.482) > Bladder cancer is the second most common malignancy in the genitourinary tract, with 350,000 newly diagnosed cases and over 145,000 deaths each year worldwide [1]. Because long-term surveillances of the patients are necessary, together with possible tumor recurrences and other complications, treatments of bladder cancers usually cost a lot of money. According to the differences in clinical developments, pathology and molecular alteration profiles, bladder cancers are classified into two types of carcinomas: the non-muscle invasive superficial, papillary carcinomas and the muscle invasive carcinomas [2]. The non-muscle invasive superficial, papillary carcinomas are usually low life-threatening, but with high incidences and high recurrences, while the muscle invasive carcinomas often cause distant metastasis and quick deaths [3]. > Multiple signaling pathways are implicated in initiation and progression of bladder cancers, including mutations in PI3K/Akt and Ras/MAPK oncogenic path way components and alterations in the tumor suppressors, such as p53 and Rb. There is increasing evidence indicating that alterations in these pathway components are not only associated with initiation of bladder cancers, but also strongly correlated with disease recurrence, progression and survival. For example, gain of function mutations of Ras, FGFR3, PIK3CA are frequently implicated in the non-muscle invasive superficial, papillary carcinomas, whereas loss of function alterations of p53 and Rb genes are found more frequently in aggressive, muscle invasive carcinomas [4][5][6]. > The phosphatidylinositol 3-kinase(PI3K) pathway regulates the balance between cell survival and apoptosis, and this balance is often disrupted in many types of human cancers, including the human urothelial bladder cancers [2]. Akt is a pivotal downstream component of the PI3K pathway, which can be activated by sequential phosphorylation at two sites conserved in the AGC kinase family [7].

[19] Protein Interactome of Muscle Invasive Bladder Cancer

  • Authors: Akshay Bhat, A. Heinzel, B. Mayer, P. Perco, Irmgard Mühlberger et al.
  • Year: 2015
  • Venue: PLoS ONE
  • URL: https://www.semanticscholar.org/paper/6253aaf68eaf05d8b09c78101b8ef90498853a50
  • DOI: 10.1371/journal.pone.0116404
  • PMID: 25569276
  • PMCID: 4287622
  • Citations: 15
  • Summary: Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder.
  • Evidence snippets:
  • Snippet 1 (score: 0.479) > Our analysis highlights the role of the cytoskeletal remodelling pathway that contains integrins, cadherins and adhesion proteins. The respective molecular pathways discussed above open new avenues for further investigation of urothelial muscle-invasive carcinoma. One enriched pathway that did not show any direct relation to bladder cancer was serotonergic synapse that contained 12 protein molecules (S3 Table ). > The bioinformatics approach reported here involved integrating available public domain data sets in context of bladder muscle-invasive carcinoma on an interaction network, and further mapping them to biological pathway sources to reveal 15 pathways as being affected in progressive disease. Eleven from these pathways were discussed previously in the context of MIBC. It should be taken into account that while using such computational techniques to integrate molecular signatures from varying resources, certain technical issues regarding the use of appropriate global identifier need to be considered. In our approach, we discarded metabolite and micro-RNA targets for the pathway enrichment analysis (i.e. gene symbols mapped from metabolomics and miRNA data, service provided by HMDB and miRBase), resulting in 592 features from the total of 1,054 protein coding genes. This is mainly driven by hampered translation of metabolite and microRNA profiles to the level of involved protein coding genes, be it on the target or enzyme level. In regard to genomics and epigenetics, we only incorporated those gene symbols that contained epigenetic information on the protein/mRNA abundance levels for the interactome analysis. > On the other hand, the two pathway terms GnHR receptor and T cell receptor signalling pathways found as enriched on the basis of the 72 gene symbols being multiply identified in, were not retrieved from the analysis resting on the full set of 286 features being derived from the induced subgraph. Data evidence and selection biases clearly affect results of such integrated analysis demanding strict quality control of input data sets as followed in our study. > Apparently, each individual functional context highlights specific aspects of bladder cancer pathophysiology, but only providing limited characterization of clinical outcome on the cohort level.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.