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

doi:10.1158/1078-0432.CCR-15-2468

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 language	English (US)
Pages (from-to)	6228-6235
Number of pages	8
Journal	Clinical Cancer Research
Volume	22
Issue number	24
DOIs	https://doi.org/10.1158/1078-0432.CCR-15-2468
State	Published - Dec 15 2016

ASJC Scopus subject areas

Oncology
Cancer Research

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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

Lee, KW, Lee, SS, Hwang, JE, Jang, HJ, Lee, HS, Oh, SC, Lee, SH, Sohn, BH, Kim, SB, Shim, JJ, Jeong, W, Cha, M, Cheong, JH, Cho, JY, Lim, JY, Park, ES, Kim, SC, Kang, YK, Noh, SH, Ajani, JA & Lee, JS 2016, 'Development and validation of a six-gene recurrence risk score assay for gastric cancer', Clinical Cancer Research, vol. 22, no. 24, pp. 6228-6235. https://doi.org/10.1158/1078-0432.CCR-15-2468

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title = "Development and validation of a six-gene recurrence risk score assay for gastric cancer",

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.",

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

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: {\textcopyright}2016 AACR.",

year = "2016",

month = dec,

day = "15",

doi = "10.1158/1078-0432.CCR-15-2468",

language = "English (US)",

volume = "22",

pages = "6228--6235",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "24",

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TY - JOUR

T1 - Development and validation of a six-gene recurrence risk score assay for gastric cancer

AU - Lee, Keun Wook

AU - Lee, Sung Sook

AU - Hwang, Jun Eul

AU - Jang, Hee Jin

AU - Lee, Hyun Sung

AU - Oh, Sang Cheul

AU - Lee, Sang Ho

AU - Sohn, Bo Hwa

AU - Kim, Sang Bae

AU - Shim, Jae Jun

AU - Jeong, Woojin

AU - Cha, Minse

AU - Cheong, Jae Ho

AU - Cho, Jae Yong

AU - Lim, Jae Yun

AU - Park, Eun Sung

AU - Kim, Sang Cheol

AU - Kang, Yoon Koo

AU - Noh, Sung Hoon

AU - Ajani, Jaffer A.

AU - Lee, Ju Seog

N1 - 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.

PY - 2016/12/15

Y1 - 2016/12/15

N2 - 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.

AB - 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.

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U2 - 10.1158/1078-0432.CCR-15-2468

DO - 10.1158/1078-0432.CCR-15-2468

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AN - SCOPUS:85006963551

SN - 1078-0432

VL - 22

SP - 6228

EP - 6235

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 24

ER -

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

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