Clinical parameters outperform molecular subtypes for predicting outcome in bladder cancer: Results from multiple cohorts including TCGA.
Authors of this article are:
Morera DS, Lahorewala SS, Belew D, Ghosh S, Klaassen Z, Jordan AR, Wang J, Terris MK, Bollag RJ, Merseburger AS, Stenzl A, Soloway MS, Lokeshwar VB.
A summary of the article is shown below:
PURPOSE: Studies report molecular subtypes within muscle invasive bladder cancer (MIBC) predict clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict clinical outcome.METHODS: Institutional cohort-1 (n=52; MIBC: 39), Oncomine-dataset (MIBC: 151) and The Cancer Genome Atlas (TCGA)-dataset (MIBC: 402) were subtyped by simplified panels (MCG-1; MCG-Ext) that included only transcripts common among published studies, and analyzed for predicting metastasis, cancer-specific survival (CSS), overall-survival (OS), and recurrence-free survival (RFS). TCGA-dataset was further analyzed using Lund-Taxonomy, BC-Molecular Taxonomy Group Consensus (Consensus), and mRNA-subtype (TCGA-2017) classifications.RESULTS: MIBC specimens from cohort-1 and Oncomine-dataset showed intra-tumor heterogeneity for transcript/protein expression. MCG-1 subtypes did not predict outcome in univariate or Kaplan-Meier analyses. In multivariate analyses, N-stage (P≤0.007), T-stage (P≤0.04), M-stage (P=0.007) and/or age (P=0.01) predicted metastasis, CSS/OS and/or cisplatin-based adjuvant-chemotherapy response. In the TCGA-dataset, publications report that subtypes risk-stratify patients for OS. Consistently, MCG-1 and MCG-Ext subtypes associated with OS, but not RFS, in univariate and Kaplan-Meier analyses. TCGA-dataset includes low-grade specimens (21/402) and subtypes associated with tumor-grade (P=0.005). However, MIBC is rarely low-grade (<1%). Among only high-grade specimens, MCG-1 and MCG-Ext subtypes could not predict OS. Subtypes by Consensus, TCGA-2017 and Lund-Taxonomy associated with tumor-grade (P<0.0001) and OS (P=0.01-<0.0001) univariately. Regardless of classification, subtypes had ∼50%-60% sensitivity and specificity to predict OS/RFS. In multivariate analyses, N-stage and lymphovascular-invasion consistently predicted RFS (P=0.039) and OS (P=0.003).CONCLUSION: Molecular subtypes reflect bladder tumor heterogeneity and associate with tumor-grade. In multiple cohorts/subtyping-classifications, clinical parameters outperform subtypes for predicting outcome.
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This article is a good source of information and a good way to become familiar with topics such as: Muscle-invasive bladder cancer; Oncomine; TCGA; molecular subtypes; tumor grade.