Please use this identifier to cite or link to this item: https://doi.org/10.7150/jca.34741
Title: Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5’UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer
Authors: Yoshikawa, T.
Aoyama, T.
Sakamaki, K.
Oshima, T.
Lin, J.
Zhang, S.
Sapari, N.S. 
Soong, R. 
Tan, I. 
Chan, X.B.
Bottomley, D.
Hewitt, L.C.
Arai, T.
Teh, B.T.
Epstein, D.
Ogata, T.
Kameda, Y.
Miyagi, Y.
Tsuburaya, A.
Morita, S.
Grabsch, H.I.
Tan, P. 
Issue Date: 2019
Publisher: Ivyspring International Publisher
Citation: Yoshikawa, T., Aoyama, T., Sakamaki, K., Oshima, T., Lin, J., Zhang, S., Sapari, N.S., Soong, R., Tan, I., Chan, X.B., Bottomley, D., Hewitt, L.C., Arai, T., Teh, B.T., Epstein, D., Ogata, T., Kameda, Y., Miyagi, Y., Tsuburaya, A., Morita, S., Grabsch, H.I., Tan, P. (2019). Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5’UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer. Journal of Cancer 10 (21) : 5130-5138. ScholarBank@NUS Repository. https://doi.org/10.7150/jca.34741
Rights: Attribution-NonCommercial 4.0 International
Abstract: Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3’UTR, and TS 5’UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5’UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5’UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series. © The author(s).
Source Title: Journal of Cancer
URI: https://scholarbank.nus.edu.sg/handle/10635/212362
ISSN: 18379664
DOI: 10.7150/jca.34741
Rights: Attribution-NonCommercial 4.0 International
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