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dc.titleComprehensive 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
dc.contributor.authorYoshikawa, T.
dc.contributor.authorAoyama, T.
dc.contributor.authorSakamaki, K.
dc.contributor.authorOshima, T.
dc.contributor.authorLin, J.
dc.contributor.authorZhang, S.
dc.contributor.authorSapari, N.S.
dc.contributor.authorSoong, R.
dc.contributor.authorTan, I.
dc.contributor.authorChan, X.B.
dc.contributor.authorBottomley, D.
dc.contributor.authorHewitt, L.C.
dc.contributor.authorArai, T.
dc.contributor.authorTeh, B.T.
dc.contributor.authorEpstein, D.
dc.contributor.authorOgata, T.
dc.contributor.authorKameda, Y.
dc.contributor.authorMiyagi, Y.
dc.contributor.authorTsuburaya, A.
dc.contributor.authorMorita, S.
dc.contributor.authorGrabsch, H.I.
dc.contributor.authorTan, P.
dc.identifier.citationYoshikawa, 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.
dc.description.abstractPurpose: 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).
dc.publisherIvyspring International Publisher
dc.rightsAttribution-NonCommercial 4.0 International
dc.sourceScopus OA2019
dc.contributor.departmentDEPT OF PATHOLOGY
dc.contributor.departmentDEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL)
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.sourcetitleJournal of Cancer
Appears in Collections:Staff Publications

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