NDA@SZTAKI

Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients.

SzĂĄsz, Attila Marcell

Lanczky, AndrĂĄs

Nagy, Ádåm

FĂśrster, Susann

Hark, Kim

SzabĂł, AndrĂĄs

Győrffy, Balázs

Impact Journals

2016

RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkolĂłgia

INTRODUCTION: 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. RESULTS: 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. MATERIALS AND METHODS: 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. CONCLUSIONS: 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.

angol

Article

PeerReviewed

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text

http://real.mtak.hu/39758/1/10337_157469_3_PB_u.pdf

Szász, Attila Marcell and Lanczky, András and Nagy, Ádám and Förster, Susann and Hark, Kim and Szabó, András and Győrffy, Balázs (2016) Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget. pp. 49322-49333. ISSN 1949-2553

http://real.mtak.hu/39758/

http://dx.doi.org/10.18632/oncotarget.10337

MTMT:3111905; doi:10.18632/oncotarget.10337