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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. Ajani  ;  Ju-Seog Lee 
 Clinical Cancer Research, Vol.22(24) : 6228-6235, 2016 
Journal Title
 Clinical Cancer Research 
Issue Date
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. Clin Cancer Res; 22(24); 6228-35. ©2016 AACR.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
노성훈(Noh, Sung Hoon) ORCID logo https://orcid.org/0000-0003-4386-6886
임재윤(Lim, Jae Yun)
정재호(Cheong, Jae Ho) ORCID logo https://orcid.org/0000-0002-1703-1781
조재용(Cho, Jae Yong) ORCID logo https://orcid.org/0000-0002-0926-1819
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