Gene Expression Signature-based Prognostic Risk Score in Gastric Cancer

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2011 Mar 31

PMID 21447720

Citations 200

Authors

Jae Yong Cho

Jae Yun Lim

Jae Ho Cheong

Yun-Yong Park

Se-Lyun Yoon

Soo Mi Kim

Sang-Bae Kim

Hoguen Kim

Soon Won Hong

Young Nyun Park

Sung Hoon Noh

Eun Sung Park

In-Sun Chu

Waun Ki Hong

Jaffer A Ajani

Ju-Seog Lee

Affiliations

Soon will be listed here.

Abstract

Purpose: Despite continual efforts to develop a prognostic model of gastric cancer by using clinical and pathologic parameters, a clinical test that can discriminate patients with good outcomes from those with poor outcomes after gastric cancer surgery has not been established. We aim to develop practical biomarker-based risk score that can predict relapse of gastric cancer after surgical treatment.

Experimental Design: Microarray technologies were used to generate and analyze gene expression profiling data from 65 gastric cancer patients to identify biomarker genes associated with relapse. The association of expression patterns of identified genes with relapse and overall survival was validated in independent gastric cancer patients.

Results: We uncovered two subgroups of gastric cancer that were strongly associated with the prognosis. For the easy translation of our findings into practice, we developed a scoring system based on the expression of six genes that predicted the likelihood of relapse after curative resection. In multivariate analysis, the risk score was an independent predictor of relapse in a cohort of 96 patients. We were able to validate the robustness of the six-gene signature in an additional independent cohort.

Conclusions: The risk score derived from the six-gene set successfully prognosticated the relapse of gastric cancer patients after gastrectomy.

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References

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M . A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004; 351(27):2817-26. DOI: 10.1056/NEJMoa041588. View

Lee J, Chu I, Mikaelyan A, Calvisi D, Heo J, Reddy J . Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nat Genet. 2004; 36(12):1306-11. DOI: 10.1038/ng1481. View

Lee J, Heo J, Libbrecht L, Chu I, Kaposi-Novak P, Calvisi D . A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med. 2006; 12(4):410-6. DOI: 10.1038/nm1377. View

Clements W, Wang J, Sarnaik A, Kim O, MacDonald J, Fenoglio-Preiser C . beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Cancer Res. 2002; 62(12):3503-6. View

Tanaka T, Tanimoto K, Otani K, Satoh K, Ohtaki M, Yoshida K . Concise prediction models of anticancer efficacy of 8 drugs using expression data from 12 selected genes. Int J Cancer. 2004; 111(4):617-26. DOI: 10.1002/ijc.20289. View

Roukos D, Kappas A . Perspectives in the treatment of gastric cancer. Nat Clin Pract Oncol. 2005; 2(2):98-107. DOI: 10.1038/ncponc0099. View

Simon R, Lam A, Li M, Ngan M, Menenzes S, Zhao Y . Analysis of gene expression data using BRB-ArrayTools. Cancer Inform. 2009; 3:11-7. PMC: 2675854. View

Landry J, Tepper J, Wood W, Moulton E, Koerner F, Sullinger J . Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys. 1990; 19(6):1357-62. DOI: 10.1016/0360-3016(90)90344-j. View

Kanta S, Yamane T, Dobashi Y, Mitsui F, Kono K, Ooi A . Topoisomerase IIalpha gene amplification in gastric carcinomas: correlation with the HER2 gene. An immunohistochemical, immunoblotting, and multicolor fluorescence in situ hybridization study. Hum Pathol. 2006; 37(10):1333-43. DOI: 10.1016/j.humpath.2006.05.008. View

10.

Simon R, Radmacher M, Dobbin K, McShane L . Pitfalls in the use of DNA microarray data for diagnostic and prognostic classification. J Natl Cancer Inst. 2003; 95(1):14-8. DOI: 10.1093/jnci/95.1.14. View

11.

Alizadeh A, Eisen M, Davis R, Ma C, Lossos I, Rosenwald A . Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403(6769):503-11. DOI: 10.1038/35000501. View

12.

Weiss M, Kuipers E, Postma C, Snijders A, Siccama I, Pinkel D . Genomic profiling of gastric cancer predicts lymph node status and survival. Oncogene. 2003; 22(12):1872-9. DOI: 10.1038/sj.onc.1206350. View

13.

Hermanek P . Prognostic factors in stomach cancer surgery. Eur J Surg Oncol. 1986; 12(3):241-6. View

14.

Heagerty P, Zheng Y . Survival model predictive accuracy and ROC curves. Biometrics. 2005; 61(1):92-105. DOI: 10.1111/j.0006-341X.2005.030814.x. View

15.

J van t Veer L, Dai H, van de Vijver M, He Y, Hart A, Mao M . Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002; 415(6871):530-6. DOI: 10.1038/415530a. View

16.

Hundahl S, Phillips J, Menck H . The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the "different disease" hypothesis. Cancer. 2000; 88(4):921-32. View

17.

Lickert H, Kispert A, Kutsch S, Kemler R . Expression patterns of Wnt genes in mouse gut development. Mech Dev. 2001; 105(1-2):181-4. DOI: 10.1016/s0925-4773(01)00390-2. View

18.

Jawhari A, Jordan S, Poole S, Browne P, Pignatelli M, Farthing M . Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival. Gastroenterology. 1997; 112(1):46-54. DOI: 10.1016/s0016-5085(97)70218-x. View

19.

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

20.

Kovoor P, Hwang J . Treatment of resectable gastric cancer: current standards of care. Expert Rev Anticancer Ther. 2008; 9(1):135-42. DOI: 10.1586/14737140.9.1.135. View