Clinical Parameters Outperform Molecular Subtypes for Predicting Outcome in Bladder Cancer: Results from Multiple Cohorts, Including TCGA.
Clinical Parameters Outperform Molecular Subtypes for Predicting Outcome in Bladder Cancer: Results from Multiple Cohorts, Including TCGA.
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DOI：
10.1097/ju.0000000000000351
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
Lokeshwar VB
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作者：
Morera DS;Hasanali SL;Belew D;Ghosh S;Klaassen Z;Jordan AR;Wang J;Terris MK;Bollag RJ;Merseburger AS;Stenzl A;Soloway MS;Lokeshwar VB
研究报告肌肉浸润性膀胱癌(MIBC)中的分子亚型预测临床结果。我们评估了简化方法的亚型和建立的分类是否可以预测临床结果。机构队列-1(n=52；MIBC：39)、肿瘤数据集(MIBC：151)和癌症基因组图谱(MIBC)数据集(MIBC：402)通过简化的面板(MCG-1；MCG-Ext)进行亚型划分，其中只包括已发表研究中常见的转录本，并分析转移、癌症特异性生存期(CSS)、总生存期(OS)和无复发生存期(RFS)。使用Lund-Taxonomy、BC-分子分类组共识(Consensus)和mRNA-亚型(TCGA-2017)分类对TCGA数据集进行进一步分析。来自Cohort-1和Oncomine数据集的MIBC样本显示肿瘤内转录/蛋白表达的异质性。在单变量或Kaplan-Meier分析中，MCG-1亚型不能预测结果。在多因素分析中，N分期(P≤0.007)、T分期(P≤0.04)、M分期(P=0.007)和/或年龄(P=0.01)预测转移、css/OS和/或顺铂辅助化疗反应。在TCGA数据集中，出版物报告了OS患者的亚型风险分层。在单变量和Kaplan-Meier分析中，一致地，MCG-1和MCG-Ext亚型与OS有关，但与RFS无关。TCGA数据集包括低级别标本(21/402)和与肿瘤分级相关的亚型(P=0.005)。然而，MIBC很少是低等级的(1%)。在仅高级别标本中，MCG-1和MCG-Ext亚型不能预测OS。亚型与肿瘤分级(P<；0.0001)和OS(P=0.0001)呈单变量相关。无论分型与否，各亚型预测OS/−的敏感度和特异度分别为50%和60%。在多因素分析中，N分期和淋巴血管侵犯一致地预测RFS(P=0.039)和OS(P=0.003)。分子亚型反映了膀胱肿瘤的异质性，并与肿瘤分级有关。在多个队列/亚型分类中，临床参数在预测结果方面优于亚型。
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. 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. 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). Molecular subtypes reflect bladder tumor heterogeneity and associate with tumor-grade. In multiple cohorts/subtyping-classifications, clinical parameters outperform subtypes for predicting outcome.