[논문]Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer

Kim, Seon-Kyu; Kim, Hee-Jin; Park, Jong-Lyul; Heo, Haejeong; Kim, Seon-Young; Lee, Sang-Il; Song, Kyu-Sang; Kim, Woo-Ho; Kim, Yong Sung

doi:10.1007/s10120-019-01029-4

[해외논문] Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer 원문보기

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, v.23 no.3, 2020년, pp.473 - 482

Kim, Seon-Kyu (Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Korea) , Kim, Hee-Jin (Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea) , Park, Jong-Lyul (Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea) , Heo, Haejeong (Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Korea) , Kim, Seon-Young (Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Korea) , Lee, Sang-Il (Department of General Surgery, College of Medicine, Chungnam National University, Daejeon, 35015 Korea) , Song, Kyu-Sang (Department of Pathology, College of Medicine, Chungnam National University, Daejeon, 35015 Korea) , Kim, Woo-Ho (Department of Pathology, Faculty of Medicine, Seoul National University, Seoul, 03080 Korea) , Kim, Yong Sung (Genome Editing Research Center, Korea)

Abstract ▼ AI-Helper

BackgroundAlthough 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.MethodsWe 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.ResultsTranscriptomic 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (10.1007/s10120-019-01029-4) contains supplementary material, which is available to authorized users.

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