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根治性膀胱切除术后用于定义肌层浸润性膀胱癌分子亚型的FOXA1基因表达

FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy.

作者信息

Sikic Danijel, Eckstein Markus, Wirtz Ralph M, Jarczyk Jonas, Worst Thomas S, Porubsky Stefan, Keck Bastian, Kunath Frank, Weyerer Veronika, Breyer Johannes, Otto Wolfgang, Rinaldetti Sebastien, Bolenz Christian, Hartmann Arndt, Wullich Bernd, Erben Philipp

机构信息

Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.

Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.

出版信息

J Clin Med. 2020 Apr 2;9(4):994. doi: 10.3390/jcm9040994.

Abstract

It remains unclear how to implement the recently revealed basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) into daily clinical routine and whether molecular marker panels can be reduced. The mRNA expression of basal (KRT5) and luminal (FOXA1, GATA3, KRT20) markers was measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and correlated to clinicopathological features, recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) in 80 patients with MIBC who underwent radical cystectomy. Additionally, the correlation of single markers with the basal and non-basal subtypes defined by a 36-gene panel was examined and then validated in the TCGA (The Cancer Genome Atlas) cohort. High expression of FOXA1 ( = 0.0048) and KRT20 ( = 0.0317) was associated with reduced RFS. In the multivariable analysis, only FOXA1 remained an independent prognostic marker for DFS ( = 0.0333) and RFS ( = 0.0310). FOXA1 expression (AUC = 0.79; = 0.0007) was closest to the combined marker expression (AUC = 0.79; = 0.0015) in resembling the non-basal subtype defined by the 36-gene panel. FOXA1 in combination with KRT5 may be used to distinguish the basal and non-basal subtypes of MIBC.

摘要

目前尚不清楚如何将最近发现的肌层浸润性膀胱癌(MIBC)的基底型和腔面型亚型应用于日常临床实践,以及分子标志物组合是否可以简化。通过逆转录定量实时聚合酶链反应(RT-qPCR)检测基底标志物(KRT5)和腔面标志物(FOXA1、GATA3、KRT20)的mRNA表达,并将其与80例行根治性膀胱切除术的MIBC患者的临床病理特征、无复发生存期(RFS)、无病生存期(DFS)和总生存期(OS)进行关联分析。此外,研究了单个标志物与由36个基因组成的基因组合所定义的基底型和非基底型亚型之间的相关性,并随后在癌症基因组图谱(TCGA)队列中进行了验证。FOXA1(P = 0.0048)和KRT20(P = 0.0317)的高表达与RFS降低相关。在多变量分析中,只有FOXA1仍然是DFS(P = 0.0333)和RFS(P = 0.0310)的独立预后标志物。FOXA1表达(AUC = 0.79;P = 0.0007)在类似于由36个基因组成的基因组合所定义的非基底型亚型方面最接近联合标志物表达(AUC = 0.79;P = 0.0015)。FOXA1与KRT5联合使用可用于区分MIBC的基底型和非基底型亚型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5763/7230662/7d248e9afc33/jcm-09-00994-g001.jpg

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