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

Iain Beehuat Tan, Tatiana Ivanova, Kiat Hon Lim, Chee Wee Ong, Niantao Deng, Julian Lee, Sze Huey Tan, Jeanie Wu, Ming Hui Lee, Chia Huey Ooi, Sun Young Rha, Wai Keong Wong, Alex Boussioutas, Khay Guan Yeoh, Jimmy So, Wei Peng Yong, Akira Tsuburaya, Heike Grabsch, Han Chong Toh, Steven RozenJae Ho Cheong, Sung Hoon Noh, Wei Kiat Wan, Jaffer A. Ajani, Juseog Lee, Manuel Salto Tellez, Patrick Tan

Research output: Contribution to journalArticlepeer-review

214 Citations (Scopus)


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-fluorouracilbased 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.

Original languageEnglish
Pages (from-to)476-485.e11
Issue number2
Publication statusPublished - 2011 Aug

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Fingerprint Dive into the research topics of 'Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy'. Together they form a unique fingerprint.

Cite this