Molecular pathways of bladder cancer

Papillary and invasive cancers of the urinary bladder appear to evolve and progress through distinct molecular pathways. Invasion in bladder cancer forebodes a graver prognosis, and these tumors are generally characterized by alterations in the p53 and retinoblastoma (RB) pathways that normally regulate the cell cycle by interacting with the Ras–mitogen activated protein kinase signal transduction pathway. Tumor angiogenesis further contributes to the neoplastic growth by providing a constant supply of oxygen and nutrients. Distinct epigenetic and genetic events characterize the interplay between the molecules involved in these pathways, thus affording their use as indicators of prognosis. Efforts are now underway to construct molecular panels comprising multiple markers that can serve as more robust predictors of outcome. While clinical trials for targeted chemotherapy for bladder cancer have commenced, novel genetic and pharmacologic agents that can target pathway-specific molecules are currently under development. The next generation of clinical management for urothelial carcinoma will witness the use of multimarker panels for prognostic prediction and combination therapy directed at novel molecular targets for treatment.

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Molecular pathways in bladder cancer

Urological Research ◽

10.1007/s00240-003-0345-y ◽

2004 ◽

Vol 32 (6) ◽

pp. 373-385 ◽

Cited By ~ 41

Author(s):

Stephen G. Williams ◽

John P. Stein

Keyword(s):

Bladder Cancer ◽

Molecular Pathways

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Differential protein expression profiling by iTRAQ-2DLC-MS/MS of human bladder cancer EJ138 cells transfected with the metastasis suppressor KiSS-1 gene

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16043 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16043-e16043

Author(s):

L. Grau ◽

I. Ruppen ◽

M. Gil ◽

J. M. Piulats ◽

J. Bellmunt ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Progression ◽

Biological Networks ◽

Molecular Mechanisms ◽

Reversed Phase ◽

Metastasis Suppressor ◽

Molecular Pathways ◽

Bladder Tumors ◽

Poor Overall Survival

e16043 Background: The use of isobaric tags for relative and absolute quantization (iTRAQ) followed by multidimensional liquid chromatography (LC) and tandem mass spectrometry (MS/MS) analysis is emerging as a powerful methodology for biomarker and drug target discovery. KiSS-1 is a metastasis suppressor gene reported to be involved in the progression of several solid neoplasias. The loss of KiSS-1 expression has been shown to be inversely correlated with increasing tumor stage and poor overall survival in bladder tumors. In order to identify the molecular pathways associated with the metastasis suppressor role of KiSS-1 in bladder cancer, we carried out a proteome discovery analysis using an iTRAQ approach. Methods: Bladder cancer cells (EJ138) were transiently transfected with a vector encompassing the full length KiSS-1 gene. Protein extracts collected after 24h and 48h transfection were fractionated, digested with trypsin and treated with iTRAQ reagents. The labelled peptides were separated through Strong Cation Exchange (SCX) and Reversed Phase LC and analysed by MALDI TOF/TOF MS. Several software packages were utilized for data analysis: ProteinPilot, Protein Center for gene ontology (GO) analysis and Ingenuity Pathway. Results: Comparative analysis among transfected, mock and empty vector exposed cells have identified more than 800 proteins with high confidence (>99%), showing high correlation rates among replicates (>70%). The involvement of the identified proteins in biological networks has served to characterize molecular pathways associated with KiSS-1 expression and to select critical candidates for validation analyses by Western Blot using independent transfected replicates. As part of complementary clinical validation strategies, inmunohistochemical analyses performed in metastatic bladder tumours spotted onto tissue microarrays (n = 175) have revealed the role of KiSS-1, ezrin and filamin in bladder cancer progression. Conclusions: Our proteomic study not only has served to reveal molecular mechanisms associated with the metastasis suppressor role of KiSS-1 in bladder cancer, but also to identify novel potential metastatic biomarkers for patients affected with bladder tumors. No significant financial relationships to disclose.

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Molecular Pathways in Low and High-grade Non-muscle Invasive Bladder Cancer as Revealed by Several OMICs Data Analyses

Precision Medicine and Clinical OMICS ◽

10.5812/pmco.115219 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Somaye Zareian ◽

Saghar Pahlavanneshan

Keyword(s):

Bladder Cancer ◽

Data Analysis ◽

Microarray Data ◽

Microarray Data Analysis ◽

Low Grade ◽

Molecular Pathways ◽

High Grade ◽

Hub Genes ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

Background: Bladder cancer is one of the most prevalent cancers, accounting for 2.1% of cancer mortalities worldwide. Bladder cancer is categorized into non-muscle invasive and muscle-invasive bladder cancers. Non-muscle invasive bladder cancer (NMIBC) is the most common and widely heterogeneous type with different outcomes. Objectives: This study was designed to categorize NMIBC tumor grade based on microarray data analysis. Methods: We performed microarray data analysis using GSE7476, GSE13507, and GSE37815 in patients diagnosed with NMIBC. Differentially expressed genes (DEGs) were identified based on low-grade and high-grade NMIBC. Protein-protein interaction (PPI) network analysis was carried out, and hub genes and underlying molecular pathways were identified. Results: We observed low-grade Hub genes, including GAS6, TGFB3, TPM1, COL5A1, COL1A2, SERPING1, ACTA2, TPM2, SDC1, and A2M involved in a variety of gene ontology (GO) biological processes, while high-grade genes were involved in cell cycle and cell division. The most relevant pathways suggested for low-grade NMIBC were extracellular matrix organization, platelet degranulation, and muscle contraction. Conclusions: The identification of gene hubs and underlying pathways in several low and high-grade NMIBC samples may offer better treatment management and prognostication based on molecular profiling.

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Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

Biomolecules ◽

10.3390/biom10081159 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1159

Author(s):

Milad Ashrafizadeh ◽

Kiavash Hushmandi ◽

Mehrdad Hashemi ◽

Mohammad Esmaeil Akbari ◽

Peter Kubatka ◽

...

Keyword(s):

Bladder Cancer ◽

Transforming Growth Factor Beta ◽

Epithelial To Mesenchymal Transition ◽

Transforming Growth Factor ◽

Molecular Pathways ◽

Mesenchymal Transition ◽

Cellular Events ◽

Number Of Factors ◽

Life Threatening

Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19–24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-β), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.

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MP36-13 DEEP SEQUENCING OF MICRORNA EXPRESSION SIGNATURE OF BLADDER CANCER: THE FUNCTIONAL SIGNIFICANCE OF MIR-145/145∗ AND ITS REGULATED MOLECULAR PATHWAYS

The Journal of Urology ◽

10.1016/j.juro.2015.02.741 ◽

2015 ◽

Vol 193 (4S) ◽

Author(s):

Satoru Inoguchi ◽

Naohiko Seki ◽

Takeshi Chiyomaru ◽

Ryosuke Matsushita ◽

Tomoaki Ishihara ◽

...

Keyword(s):

Bladder Cancer ◽

Deep Sequencing ◽

Functional Significance ◽

Microrna Expression ◽

Molecular Pathways ◽

Expression Signature

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Validation of activated molecular pathways in non-T cell-inflamed urothelial bladder cancer (UBC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e23114 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e23114-e23114

Author(s):

Randy F. Sweis ◽

Riyue Bao ◽

Stefani Spranger ◽

Gladell Paner ◽

Walter Michael Stadler ◽

...

Keyword(s):

Bladder Cancer ◽

T Cell ◽

Molecular Pathways ◽

Urothelial Bladder Cancer ◽

Urothelial Bladder

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Urinary bladder cancer: biomarkers and target therapy, new era for more attention

Oncology Reviews ◽

10.4081/oncol.2016.320 ◽

2016 ◽

Cited By ~ 11

Author(s):

Amrallah A. Mohammed ◽

Hani EL-Tanni ◽

Hani M. EL-Khatib ◽

Ahmad A. Mirza ◽

Abdulrahim A. Mirza ◽

...

Keyword(s):

Bladder Cancer ◽

Target Therapy ◽

Urinary Bladder Cancer ◽

Cancer Biomarkers ◽

Tumor Stage ◽

Clinicopathological Parameters ◽

Molecular Pathways ◽

New Era ◽

Molecular Alterations ◽

Non Invasive

Currently, bladder cancer (BCa) evaluation depends mainly on traditional clinicopathological parameters encompassing tumor stage and grade, which will not reflect the behavior of the disease. Diverse molecular alterations are responsible for the heterogeneous course. The differences in molecular pathogenesis between non-invasive BCa and invasive BCa have been recognized. Molecular biomarkers are promising to predict progression and survival. The management of advanced BCa remains somewhat primitive in comparison with other more common malignancies. This topic will discuss the molecular pathways, biomarkers and potential targets that may improve the outcome in BCa.

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