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

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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

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lee, K. W., Lee, S. S., Hwang, J. E., Jang, H. J., Lee, H. S., Oh, S. C., Lee, S. H., Sohn, B. H., Kim, S. B., Shim, J. J., Jeong, W., Cha, M., Cheong, J. H., Cho, J. Y., Lim, J. Y., Park, E. S., Kim, S. C., Kang, Y. K., Noh, S. H., ... Lee, J. S. (2016). Development and validation of a six-gene recurrence risk score assay for gastric cancer. Clinical Cancer Research, 22(24), 6228-6235. https://doi.org/10.1158/1078-0432.CCR-15-2468