Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients.
Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients.
复制标题
DOI：
10.18632/oncotarget.10337
复制
发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Győrffy B
中科院分区：
文献类型：
--
作者：
Szász AM;Lánczky A;Nagy Á;Förster S;Hark K;Green JE;Boussioutas A;Busuttil R;Szabó A;Győrffy B
基于多种基因表达的预后生物标志物在胃癌中已被反复鉴定。然而，由于没有独立验证研究的确认，其临床实用性有限。我们的目标是建立一个强大的数据库，使以前和未来的胃癌生存生物标志物候选人的快速验证。整个数据库收录了1,065例胃癌样本的基因表达数据。在29个已建立的标志物中，BECN 1的表达较高，（HR = 0.68，p = 1.5E-05），CASP3（HR = 0.5，p = 6E-14），COX 2（HR = 0.72，p = 0.0013），CTGF（HR = 0.72，p = 0.00051），CTNNB1（HR = 0.47，p = 4.3E-15），MET（HR = 0.63，p = 1.3E-05）和SIRT 1（HR = 0.64，p = 2.2E-07）与更长的OS相关。（HR = 1.45，p = 1E-04），CNTN 1（HR = 1.44，p = 3.5E- 05），EGFR（HR = 1.86，p = 8.5E-11），ERCC1（HR = 1.36，p = 0.0012），HER2（HR = 1.41，p = 0.00011），MMP 2（HR = 1.78，p = 2.6E-09），PFKB 4（HR = 1.56，p = 3.2E-07），SPHK1（HR = 1.61，p = 3.1E-06），SP1（HR = 1.45，p = 1.6E-05），TIMP 1（HR = 1.92，p = 2.2E- 10）和VEGF（HR = 1.53，p = 5.7E-06）预测OS较差。我们整合了三个主要癌症研究中心的样本（柏林、贝塞斯达和墨尔本数据集）和公开可用的数据集以及可用的随访数据，以形成一个单一的综合数据库。随后，我们对胃癌预后标志物进行了文献检索（PubMed，2012-2015），并使用单因素和多因素考克斯比例风险回归分析重新验证了其预测首次进展（FP）和总生存期（OS）的结果。我们的分析的主要优点是，我们评估了同一组患者中的所有基因，从而使标记物的直接比较可行。表现最好的基因包括BIRC 5、CASP 3、CTNNB 1、TIMP-1、MMP-2、SIRT和VEGF。
Multiple gene expression based prognostic biomarkers have been repeatedly identified in gastric carcinoma. However, without confirmation in an independent validation study, their clinical utility is limited. Our goal was to establish a robust database enabling the swift validation of previous and future gastric cancer survival biomarker candidates. The entire database incorporates 1,065 gastric carcinoma samples, gene expression data. Out of 29 established markers, higher expression of BECN1 (HR = 0.68, p = 1.5E-05), CASP3 (HR = 0.5, p = 6E-14), COX2 (HR = 0.72, p = 0.0013), CTGF (HR = 0.72, p = 0.00051), CTNNB1 (HR = 0.47, p = 4.3E-15), MET (HR = 0.63, p = 1.3E-05), and SIRT1 (HR = 0.64, p = 2.2E-07) correlated to longer OS. Higher expression of BIRC5 (HR = 1.45, p = 1E-04), CNTN1 (HR = 1.44, p = 3.5E- 05), EGFR (HR = 1.86, p = 8.5E-11), ERCC1 (HR = 1.36, p = 0.0012), HER2 (HR = 1.41, p = 0.00011), MMP2 (HR = 1.78, p = 2.6E-09), PFKB4 (HR = 1.56, p = 3.2E-07), SPHK1 (HR = 1.61, p = 3.1E-06), SP1 (HR = 1.45, p = 1.6E-05), TIMP1 (HR = 1.92, p = 2.2E- 10) and VEGF (HR = 1.53, p = 5.7E-06) were predictive for poor OS. We integrated samples of three major cancer research centers (Berlin, Bethesda and Melbourne datasets) and publicly available datasets with available follow-up data to form a single integrated database. Subsequently, we performed a literature search for prognostic markers in gastric carcinomas (PubMed, 2012–2015) and re-validated their findings predicting first progression (FP) and overall survival (OS) using uni- and multivariate Cox proportional hazards regression analysis. The major advantage of our analysis is that we evaluated all genes in the same set of patients thereby making direct comparison of the markers feasible. The best performing genes include BIRC5, CASP3, CTNNB1, TIMP-1, MMP-2, SIRT, and VEGF.