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Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy

Title
 Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy
Authors
 Sung Hoon Noh; Wei Kiat Wan; Jae Ho Cheong; Steven Rozen; Han Chong Toh; Heike Grabsch; Akira Tsuburaya; Wei Peng Yong; Jimmy So; Khay Guan Yeoh; Alex Boussioutas; Wai Keong Wong; Sun Young Rha; Chia Huey Ooi; Ming Hui Lee; Jeanie Wu; Sze Huey Tan; Julian Lee; Niantao Deng; Chee Wee Ong; Kiat Hon Lim; Tatiana Ivanova; Iain Beehuat Tan; Jaffer A. Ajani; Ju-Seog Lee; Manuel Salto Tellez; Patrick Tan
Issue Date
2011
Journal Title
 Gastroenterology
ISSN
 0016-5085
Citation
 Gastroenterology , Vol.141(2) : 476~485,485.e1-11., 2011
Abstract
BACKGROUND & AIMS: Gastric cancer (GC) is a heterogeneous disease comprising multiple subtypes that have distinct biological properties and effects in patients. We sought to identify new, intrinsic subtypes of GC by gene expression analysis of a large panel of GC cell lines. We tested if these subtypes might be associated with differences in patient survival times and responses to various standard-of-care cytotoxic drugs. METHODS: We analyzed gene expression profiles for 37 GC cell lines to identify intrinsic GC subtypes. These subtypes were validated in primary tumors from 521 patients in 4 independent cohorts, where the subtypes were determined by either expression profiling or subtype-specific immunohistochemical markers (LGALS4, CDH17). In vitro sensitivity to 3 chemotherapy drugs (5-fluorouracil, cisplatin, oxaliplatin) was also assessed. RESULTS: Unsupervised cell line analysis identified 2 major intrinsic genomic subtypes (G-INT and G-DIF) that had distinct patterns of gene expression. The intrinsic subtypes, but not subtypes based on Lauren's histopathologic classification, were prognostic of survival, based on univariate and multivariate analysis in multiple patient cohorts. The G-INT cell lines were significantly more sensitive to 5-fluorouracil and oxaliplatin, but more resistant to cisplatin, than the G-DIF cell lines. In patients, intrinsic subtypes were associated with survival time following adjuvant, 5-fluorouracil-based therapy. CONCLUSIONS: Intrinsic subtypes of GC, based on distinct patterns of expression, are associated with patient survival and response to chemotherapy. Classification of GC based on intrinsic subtypes might be used to determine prognosis and customize therapy.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/94468
DOI
10.1053/j.gastro.2011.04.042.
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Dept. of Surgery
Yonsei Authors
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