FGFR3 Mutation Status and FGFR3 Expression in a Large Bladder Cancer Cohort Treated by Radical Cystectomy: Implications for Anti-FGFR3 Treatment?†

Rhijn, Bas W.G. van; Mertens, Laura S.; Mayr, Roman; Boström, Peter J.; Real, Francisco X.; Zwarthoff, Ellen C.; Boormans, Joost L.; Abas, Cheno; Leenders, Geert J.L.H. van; Götz, Stefanie; Hippe, Katrin; Bertz, Simone; Neuzillet, Y.; Sanders, Joyce; Broeks, Annegien; Heijden, Michiel S. van der; Jewett, Michael A.S.; Márquez, Mirari; Stoehr, Robert; Zlotta, Alexandre R.; Eckstein, Markus; Soorojebally, Yanish; Roshani, Hossain; Burger, Maximilian; Otto, Wolfgang; Radvanyi, François; Sirab, Nanor; Pouessel, Damien; Wullich, Bernd; Kwast, Theo H. van der; Malats, Núria; Hartmann, Arndt; Allory, Yves; Zuiverloon, Tahlita C.M.

doi:10.1016/j.eururo.2020.07.002

Cited by 64 publications

(57 citation statements)

References 10 publications

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“…We con rmed that one of the most prominent biological characteristics was the signi cant change in FGFR3, including mutations and overexpression, and a signi cant increase in FGFR3 gene mutations in cluster A. Previous studies have con rmed that FGFR oncogenic mutations occur in a fth of bladder cancers [42,43]. The protein encoded by FGFR3 is a member of the FGFR family and is related to Ras protein kinase/mitogen-activated protein kinase activation, angiogenesis inhibition, broblast activation, and EMT [44].…”

Section: Discussionsupporting

confidence: 55%

Analysis of tumor microenvironment characteristics in bladder cancer: implications for immune checkpoint inhibitor therapy

Chen

et al. 2021

Preprint

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Background The tumor microenvironment (TME) has a significant influence on prognosis and immunotherapy. There are no studies on the systematic analysis of bladder cancer TME and its effect on immune checkpoint inhibitor therapy. Methods We comprehensively evaluated the TME infiltration pattern of bladder cancer in 1,889 patients and conducted extensive immunogenomic analysis to explore the heterogeneity and prognostic significance of the TME of bladder cancer. The principal component analysis algorithm was used to calculate the immune cell (IC)score to quantify the level of IC infiltration. We used the receiver operating characteristic (ROC) curve, Tumor Immune Dysfunction and Exclusion (TIDE), and Subnetwork Mappings in Alignment of Pathways (SubMAP) algorithms to evaluate whether the ICscore can predict the benefits of immune checkpoint inhibitors in bladder cancer patients. Results We identified three different TME phenotypes using unsupervised clustering methods. To explore the potential biological pathways that drive the formation of these microenvironmental phenotypes, we demonstrated the clinical and pathological characteristics, biological signaling pathways, cancer immune circulation, copy number, and somatic mutation differences among the different subtypes. In addition, univariate and multivariate Cox regression analyses showed that the ICscore is a reliable and independent prognostic marker. The ICscore can also predict immune checkpoint inhibitor responsiveness as patients with higher ICscores showed a significant therapeutic advantage in immunotherapy. Conclusions This study increases our understanding of the characteristics of TME infiltration in bladder cancer and provides guidance on more effective personalized immunotherapeutic strategies.

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Section: Discussionsupporting

confidence: 55%

Analysis of tumor microenvironment characteristics in bladder cancer: implications for immune checkpoint inhibitor therapy

Chen

et al. 2021

Preprint

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“…Therefore, further study on the mechanism of progression, recurrence and metastasis of BLCA is the focus of clinical research. 11 A large number of relevant studies have shown that the changes of gene expressions can significantly affect the progression of BLCA, such as transcription factor GATA-binding factor 6 (GATA6), 12 stromal antigen 2 (STAG2), 13 BCL2L2-PABPN1 and CHFR-GOLGA3, 14 growth arrest-specific transcript 5 (GAS5), 15 fibroblast growth factor receptor 3 (FGFR3) 16 and lymph node metastasis associated transcript 1 (LNMAT1). 17 α-E-catenin (CTNNA1) is considered to be an important protein connecting the E-Cadherin/ β-catenin.…”

Section: Introductionmentioning

confidence: 99%

<p>α-E-Catenin (CTNNA1) Inhibits Cell Proliferation, Invasion and EMT of Bladder Cancer</p>

Chi¹,

Xu²,

Song³

et al. 2020

CMAR

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Aim Bladder cancer (BLCA) is an urogenital system tumor with a high morbidity. We aimed to explore the function and potential mechanism of α-E-catenin (CTNNA1) in BLCA. Methods The CTNNA1 expression in BLCA tissues was detected using qRT-PCR and immunohistochemistry. QRT-PCR and Western blot were performed to measure the CTNNA1 expression in BLCA cell lines. CTNNA1 expression was up-regulated in T24 and UMUC-2 cells by CTNNA1 overexpression plasmid transfection. Cell proliferation, apoptosis, migration and invasion were respectively assessed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. The expression levels of epithelial–mesenchymal transition (EMT)-related factors were tested by qRT-PCR and Western blot. BLCA nude mice models were constructed to explore the effects of CTNNA1 on BLCA in vivo. Gene set enrichment analysis (GSEA) was proceeded to identify the CTNNA1-related pathways in BLCA. Results The expressions of CTNNA1 were down-regulated in BLCA tissues and cell lines, and its low expression indicated poor prognosis of BLCA patients. CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA cells. CTNNA1 enhanced E-cadherin expression and suppressed N-cadherin, snail, MMP2 and MMP9 expressions in BLCA cells, which suggested that CTNNA1 repressed EMT in BLCA cells. Moreover, CTNNA1 could inhibit tumor growth in vivo. CTNNA1 was positively associated with P53 and apoptosis pathways in BLCA cells. Conclusion CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA via activating P53 and apoptosis pathways. CTNNA1 might be a novel target in BLCA therapy.

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“…The oncogenes associated with bladder cancer include HER-2, H-RAS, Bcl-2, FGFR3, C-MYC, C-Erbb-2, MDM2, CDC91L1, etc. [10][11][12][13][14][15][16] Hypermethylation of SYK, CAGE-1 and other genes has been associated with the progression of bladder cancer [10,11]. In addition, the occurrence of bladder cancer also includes the ampli cation or overexpression of normal genes encoding growth factors or their receptors [16,17], for example, the overexpression of EGEF can increase the aggressiveness and metastasis of bladder cancer [18].…”

Section: Discussionmentioning

confidence: 99%

TCGA data mining suggested that high GSDMB expression in bladder cancer indicated an excellent prognosis

Xu¹,

Tang²,

Zhang³

2020

Preprint

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Background. Researchers have demonstrated that GSDMB is highly expressed in cancer tissues and located in amplicons, genomic regions that are often amplified during cancer development. We evaluated the role of GSDMB in bladder cancer using publicly available data.Methods. The relationship between clinical correlation features and GSDMB were analyzed with the Wilcoxon rank sum test (2 groups), Kruskal-Wallis test (multiple groups) and logistic regression. Clinicopathologic characteristics associated with overall survival in TCGA patients using Cox regression and the Kaplan-Meier method. Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. Results. GSDMB was differentially expressed between the tumor group and the normal group and was highly expressed in the tumor group. Reduced GSDMB expression in BLCA as significantly associated with grade (OR = 4.55, High Grade vs. Low Grade), clinical stage (OR = 2.34, Ⅱvs. Ⅳ), status (OR = 0.51 survival vs. death), all p-values <0.05. Kaplan-Meier survival analysis showed that BLCA with GSDMB- low had a worse prognosis than that with GSDMB-high (p = 0.001). The univariate analysis revealed that GSDMB- low correlated significantly with a poor overall survival (OS) (HR: 0.93; 95%CI: 0.89-0,98; p = 0.006). The multivariate analysis revealed that GSDMB remained independently associated with overall survival, with a HR of 0.711 (CI: 0.55-0.92; p = 0.009). GSEA show that focal adhesion, pathways in cancer, small cell lung cancer, renal cell carcinoma, bladder cancer and other cancer related pathways are differentially enriched in GSDMB low expression phenotype. Conclusions. High GSDMB mRNA expression is an independent risk factor for excellent prognosis in bladder cancer.

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FGFR3 Mutation Status and FGFR3 Expression in a Large Bladder Cancer Cohort Treated by Radical Cystectomy: Implications for Anti-FGFR3 Treatment?†

Cited by 64 publications

References 10 publications

Analysis of tumor microenvironment characteristics in bladder cancer: implications for immune checkpoint inhibitor therapy

Analysis of tumor microenvironment characteristics in bladder cancer: implications for immune checkpoint inhibitor therapy

<p>α-E-Catenin (CTNNA1) Inhibits Cell Proliferation, Invasion and EMT of Bladder Cancer</p>

TCGA data mining suggested that high GSDMB expression in bladder cancer indicated an excellent prognosis

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