Development and validation of a six-gene recurrence risk score assay for gastric cancer

Keun Wook Lee, Sung Sook Lee, Jun Eul Hwang, Hee Jin Jang, Hyun Sung Lee, Sang Cheul Oh, Sang Ho Lee, Bo Hwa Sohn, Sang Bae Kim, Jae Jun Shim, Woojin Jeong, Minse Cha, Jae Ho Cheong, Jae Yong Cho, Jae Yun Lim, Eun Sung Park, Sang Cheol Kim, Yoon Koo Kang, Sung Hoon Noh, Jaffer A. AjaniJu Seog Lee

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Purpose: This study was aimed at developing and validating a quantitative multigene assay for predicting tumor recurrence after gastric cancer surgery. Experimental Design: Gene expression data were generated from tumor tissues of patients who underwent surgery for gastric cancer (n = 267, training cohort). Genes whose expression was significantly associated with activation of YAP1 (a frequently activated oncogene in gastrointestinal cancer), 5-year recurrence-free survival, and 5-year overall survival were first identified as candidates for prognostic genes (156 genes, P < 0.001). We developed the recurrence risk score (RRS) by using quantitative RT-PCR to identify genes whose expression levels were significantly associated with YAP1 activation and patient survival in the training cohort. Results: We based the RRS assay on 6 genes, IGFBP4, SFRP4, SPOCK1, SULF1, THBS, and GADD45B, whose expression levels were significantly associated with YAP1 activation and prognosis in the training cohort. The RRS assay was further validated in an independent cohort of 317 patients. In multivariate analysis, the RRS was an independent predictor of recurrence [HR, 1.6; 95% confidence interval (CI), 1.02-2.4; P = 0.03]. In patients with stage II disease, the RRS had an HR of 2.9 (95% CI, 1.1-7.9; P = 0.03) and was the only significant independent predictor of recurrence. Conclusions: The RRS assay was a valid predictor of recurrence in the two cohorts of patients with gastric cancer. Independent prospective studies to assess the clinical utility of this assay are warranted.

Original languageEnglish
Pages (from-to)6228-6235
Number of pages8
JournalClinical Cancer Research
Volume22
Issue number24
DOIs
Publication statusPublished - 2016 Dec 15

Bibliographical note

Funding Information:
This research was supported by grants from the NIH (CA127672, CA129906, CA138671, CA 172741, and CA150229); 2016 Institutional Research Grant (IRG) and 2016 Sister Institute Network Fund (SINF) grant from The University of Texas MD Anderson Cancer Center; Bio and Medical Technology Development Program (M10642040002-07N4204-00210); Scientific Research Center Program (2012R1A5A1048236); Korea National Research Foundation (No. 2014M3C1A3051981); and Research Initiative grant from Korean Research Institute of Bioscience and Biotechnology (KRIBB). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Publisher Copyright:
©2016 AACR.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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