Identifcation of a molecular signature of prognostic subtypes in difuse-type gastric cancer

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dc.contributor.authorSeon-Kyu Kim-
dc.contributor.authorHee Jin Kim-
dc.contributor.authorJong Lyul Park-
dc.contributor.authorHaejeong Heo-
dc.contributor.authorSeon-Young Kim-
dc.contributor.authorS I Lee-
dc.contributor.authorK S Song-
dc.contributor.authorW H Kim-
dc.contributor.authorYong Sung Kim-
dc.date.accessioned2020-04-24T16:30:40Z-
dc.date.available2020-04-24T16:30:40Z-
dc.date.issued2020-
dc.identifier.issn1436-3291-
dc.identifier.uri10.1007/s10120-019-01029-4ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/19460-
dc.description.abstractBACKGROUND: Although recent advances in high-throughput technology have provided many insights into gastric cancer (GC), few reliable biomarkers for diffuse-type GC have been identified. Here, we aim to identify a prognostic and predictive signature of diffuse-type GC heterogeneity. METHODS: We analyzed RNA-seq-based transcriptome data to identify a molecular signature in 150 gastric tissue samples including 107 diffuse-type GCs. The predictive value of the signature was verified using other diffuse-type GC samples in three independent cohorts (n=466). Log-rank and Cox regression analyses were used to estimate the association between the signature and prognosis. The signature was also characterized by somatic variant analyses and tissue microarray analysis between diffuse-type GC subtypes. RESULTS: Transcriptomic profiling of RNA-seq data identified a signature which revealed distinct subtypes of diffuse-type GC: the intestinal-like (INT) and core diffuse-type (COD) subtypes. The signature showed high predictability and independent clinical utility in diffuse-type GC prognosis in other patient cohorts (HR 2.058, 95% CI 1.53-2.77, P=1.76×10 -6). Integrative mutational and gene expression analyses demonstrated that the COD subtype was responsive to chemotherapy, whereas the INT subtype was responsive to immunotherapy with an immune checkpoint inhibitor (ICI). Tissue microarray analysis showed the practical utility of IGF1 and NXPE2 for predicting diffuse-type GC heterogeneity. CONCLUSIONS: We present a molecular signature that can identify diffuse-type GC patients who display different clinical behaviors as well as responses to chemotherapy or ICI treatment.-
dc.publisherSpringer-
dc.titleIdentifcation of a molecular signature of prognostic subtypes in difuse-type gastric cancer-
dc.title.alternativeIdentifcation of a molecular signature of prognostic subtypes in difuse-type gastric cancer-
dc.typeArticle-
dc.citation.titleGastric Cancer-
dc.citation.number0-
dc.citation.endPage482-
dc.citation.startPage473-
dc.citation.volume23-
dc.contributor.affiliatedAuthorSeon-Kyu Kim-
dc.contributor.affiliatedAuthorHee Jin Kim-
dc.contributor.affiliatedAuthorJong Lyul Park-
dc.contributor.affiliatedAuthorHaejeong Heo-
dc.contributor.affiliatedAuthorSeon-Young Kim-
dc.contributor.affiliatedAuthorYong Sung Kim-
dc.contributor.alternativeName김선규-
dc.contributor.alternativeName김희진-
dc.contributor.alternativeName박종열-
dc.contributor.alternativeName허해정-
dc.contributor.alternativeName김선영-
dc.contributor.alternativeName이상일-
dc.contributor.alternativeName송규상-
dc.contributor.alternativeName김우호-
dc.contributor.alternativeName김용성-
dc.identifier.bibliographicCitationGastric Cancer, vol. 23, pp. 473-482-
dc.identifier.doi10.1007/s10120-019-01029-4-
dc.subject.keywordChemotherapy-
dc.subject.keywordDiffuse-type GC-
dc.subject.keywordGastric cancer-
dc.subject.keywordImmune checkpoint inhibitor-
dc.subject.keywordPrognosis-
dc.subject.localChemotherapy-
dc.subject.localchemotherapy-
dc.subject.localDiffuse-type GC-
dc.subject.localgastric cancer-
dc.subject.localGastric cancer (GC)-
dc.subject.localGastric cancer-
dc.subject.localimmune checkpoint inhibitor-
dc.subject.localImmune checkpoint inhibitor-
dc.subject.localImmune check-point inhibitor-
dc.subject.localPrognosis-
dc.subject.localprognosis-
dc.description.journalClassY-
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Aging Convergence Research Center > 1. Journal Articles
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