A review of molecular biomarkers for bladder cancer

Miakhil, Iqbal; Parker, Stuart G.; Kommu, SS; Nethercliffe, J

doi:10.14194/ijmbr.235

Cited by 2 publications

(2 citation statements)

References 52 publications

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“…For instance, Nuclear Matrix Protein-22 (NMP-22), a protein component found in the spindle of mitotic cells, could ensure chromosome segregation when cells underwent mitosis. A small amount of NMP-22 could be found in the urine of normal people, and BC might exist when its content exceeded the threshold (Miakhil et al, 2013). However, the sensitivity and specificity of NMP-22 were reported controversially in literatures (47–90%) (Tilki et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer

Yan

Guo

et al. 2019

Front. Genet.

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Given that most bladder cancers (BCs) are diagnosed in advanced stages with poor prognosis, this study aims to find novel biomarkers associated with the progression and prognosis in patients with BC. 1,779 differentially expressed genes (DEGs) between BC samples and normal bladder tissues were identified in total. Then, 24 DEGs were regarded as candidate hub genes by constructing a protein–protein interaction (PPI) network and a random forest model. Among them, six genes (BUB1B, CCNB1, CDK1, ISG15, KIF15, and RAD54L) were eventually identified by using five analysis methods (one-way Analysis of Variance analysis, spearman correlation analysis, distance correlation analysis, receiver operating characteristic curve, and expression values comparison), which were correlated with the progression and prognosis of BC. Moreover, the validation of hub genes was conducted based on GSE13507, Oncomine, and CBioPortal. Results of univariate Cox regression analysis showed that the expression levels of all the hub genes were influence features of overall survival (OS) and cancer specific survival (CSS) based on GSE13507, and we further established a six-gene signature based on the expression levels of the six genes and their Cox regression coefficients. This signature showed good potential for clinical application suggested by survival analysis (OS: Hazard Ratio = 0.484, 95%CI: 0.298–0.786; P = 0.0034; CSS: Hazard Ratio = 0.244, 95%CI: 0.121–0.493, P < 0.0001) and decision curve analysis. In conclusion, our study indicates that six hub genes have great predictive value for the prognosis and progression of BC and may contribute to the exploration of further basic and clinical research of BC.

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Section: Introductionmentioning

confidence: 99%

Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer

Yan

Guo

et al. 2019

Front. Genet.

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“…MIBC treatment includes cystectomy and (neo)adjuvant cisplatin-based chemotherapy regimens [ 2 ]. However, significant variations in the natural history of the disease and responses to treatment can be observed between tumours with identical histological features, reflecting their high molecular heterogeneity [ 3 ]. Furthermore, approximately 50% of cases develop metastasis within 5 years, urging the identification of biomarkers to assist prognostication and the development of more effective targeted therapeutics [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Abnormal Protein Glycosylation and Activated PI3K/Akt/mTOR Pathway: Role in Bladder Cancer Prognosis and Targeted Therapeutics

et al. 2015

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Muscle invasive bladder cancer (MIBC, stage ≥T2) is generally associated with poor prognosis, constituting the second most common cause of death among genitourinary tumours. Due to high molecular heterogeneity significant variations in the natural history and disease outcome have been observed. This has also delayed the introduction of personalized therapeutics, making advanced stage bladder cancer almost an orphan disease in terms of treatment. Altered protein glycosylation translated by the expression of the sialyl-Tn antigen (STn) and its precursor Tn as well as the activation of the PI3K/Akt/mTOR pathway are cancer-associated events that may hold potential for patient stratification and guided therapy. Therefore, a retrospective design, 96 bladder tumours of different stages (Ta, T1-T4) was screened for STn and phosphorylated forms of Akt (pAkt), mTOR (pmTOR), S6 (pS6) and PTEN, related with the activation of the PI3K/Akt/mTOR pathway. In our series the expression of Tn was residual and was not linked to stage or outcome, while STn was statically higher in MIBC when compared to non-muscle invasive tumours (p = 0.001) and associated decreased cancer-specific survival (log rank p = 0.024). Conversely, PI3K/Akt/mTOR pathway intermediates showed an equal distribution between non-muscle invasive bladder cancer (NMIBC) and MIBC and did not associate with cancer-specif survival (CSS) in any of these groups. However, the overexpression of pAKT, pmTOR and/or pS6 allowed discriminating STn-positive advanced stage bladder tumours facing worst CSS (p = 0.027). Furthermore, multivariate Cox regression analysis revealed that overexpression of PI3K/Akt/mTOR pathway proteins in STn+ MIBC was independently associated with approximately 6-fold risk of death by cancer (p = 0.039). Mice bearing advanced stage chemically-induced bladder tumours mimicking the histological and molecular nature of human tumours were then administrated with mTOR-pathway inhibitor sirolimus (rapamycin). This decreased the number of invasive lesions and, concomitantly, the expression of STn and also pS6, the downstream effector of the PI3K/Akt/mTOR pathway. In conclusion, STn was found to be marker of poor prognosis in bladder cancer and, in combination with PI3K/Akt/mTOR pathway evaluation, holds potential to improve the stratification of stage disease. Animal experiments suggest that mTOR pathway inhibition could be a potential therapeutic approach for this specific subtype of MIBC.

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A review of molecular biomarkers for bladder cancer

Cited by 2 publications

References 52 publications

Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer

Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer

Abnormal Protein Glycosylation and Activated PI3K/Akt/mTOR Pathway: Role in Bladder Cancer Prognosis and Targeted Therapeutics

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