Lee Hsiang-Ying, Li Ching-Chia, Huang Chun-Nung, Li Wei-Ming, Yeh Hsin-Chih, Ke Hung-Lung, Yang Kai-Fu, Liang Peir-In, Li Chien-Feng, Wu Wen-Jeng
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
J Surg Oncol. 2015 Mar 15;111(4):414-22. doi: 10.1002/jso.23836. Epub 2014 Dec 9.
Urothelial carcinoma (UC) originating from the bladder (UBUC) and upper urinary tract (UTUC) is the most common type of urinary tract tumor. While its pathogenesis remains obscured. Computerizing a published transcriptomic database of UBUC (GSE31684), we identified Inhibin, Beta A (INHBA) as the most significant upregulated gene associated with tumor progression among those associated with growth factor activity (GO:0008083). We therefore analyzed the clinicopathological significance of INHBA expression in UC.
QuantiGene assay was used to detect INHBA transcript level in 36 UTUCs and 30 UBUCs. Immunohistochemistry evaluated by H-score was used to determine INHBA protein expression in 340 UTUCs and 296 UBUCs. INHBA expression was correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS).
Increments of INHBA transcript level was associated with higher pT status in both UTUC and UBUC. INHBA protein overexpression was significantly associated with advanced clinicopathological features in both groups of UC. INHBA overexpression significantly implied inferior DSS (UTUC, P = 0.002; UBUC, P = 0.005) and MeFS (UTUC and UBUC, both P < 0.001) in multivariate analysis.
INHBA overexpression implies adverse clinical outcomes for UC, justifying it is a potential prognostic biomarker and a novel therapeutic target in UC.
起源于膀胱（UBUC）和上尿路（UTUC）的尿路上皮癌（UC）是最常见的尿路肿瘤类型。但其发病机制仍不清楚。通过将已发表的UBUC转录组数据库（GSE31684）电子化，我们确定抑制素βA（INHBA）是与肿瘤进展相关的、在与生长因子活性相关的基因（GO:0008083）中上调最显著的基因。因此，我们分析了INHBA在UC中的表达的临床病理意义。
采用QuantiGene检测法检测36例UTUC和30例UBUC中的INHBA转录水平。采用免疫组化H评分法评估340例UTUC和296例UBUC中的INHBA蛋白表达。将INHBA表达与临床病理特征、疾病特异性生存（DSS）和无转移生存（MeFS）进行关联分析。
在UTUC和UBUC中，INHBA转录水平的升高均与较高的pT分期相关。在两组UC中，INHBA蛋白过表达均与晚期临床病理特征显著相关。多因素分析显示，INHBA过表达显著提示DSS较差（UTUC，P = 0.002；UBUC，P = 0.005）和MeFS较差（UTUC和UBUC，P均<0.001）。
INHBA过表达提示UC预后不良，证明其是UC潜在的预后生物标志物和新的治疗靶点。
