PT - JOURNAL ARTICLE AU - Suling J Lin AU - Johann A Gagnon-Bartsch AU - Iain Beehuat Tan AU - Sophie Earle AU - Louise Ruff AU - Katherine Pettinger AU - Bauke Ylstra AU - Nicole van Grieken AU - Sun Young Rha AU - Hyun Cheol Chung AU - Ju-Seog Lee AU - Jae Ho Cheong AU - Sung Hoon Noh AU - Toru Aoyama AU - Yohei Miyagi AU - Akira Tsuburaya AU - Takaki Yoshikawa AU - Jaffer A Ajani AU - Alex Boussioutas AU - Khay Guan Yeoh AU - Wei Peng Yong AU - Jimmy So AU - Jeeyun Lee AU - Won Ki Kang AU - Sung Kim AU - Yoichi Kameda AU - Tomio Arai AU - Axel zur Hausen AU - Terence P Speed AU - Heike I Grabsch AU - Patrick Tan TI - Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas AID - 10.1136/gutjnl-2014-308252 DP - 2015 Nov 01 TA - Gut PG - 1721--1731 VI - 64 IP - 11 4099 - http://gut.bmj.com/content/64/11/1721.short 4100 - http://gut.bmj.com/content/64/11/1721.full SO - Gut2015 Nov 01; 64 AB - Objective Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome.Design We compared gene expression profiles of 1016 GCs from six Asian and three non-Asian GC cohorts, using a two-stage meta-analysis design and a novel biostatistical method (RUV-4) to adjust for technical variation between cohorts. We further validated our findings by computerised immunohistochemical analysis on two independent tissue microarray (TMA) cohorts from Asian and non-Asian localities (n=665).Results Gene signatures differentially expressed between Asians and non-Asian GCs were related to immune function and inflammation. Non-Asian GCs were significantly enriched in signatures related to T-cell biology, including CTLA-4 signalling. Similarly, in the TMA cohorts, non-Asian GCs showed significantly higher expression of T-cell markers (CD3, CD45R0, CD8) and lower expression of the immunosuppressive T-regulatory cell marker FOXP3 compared to Asian GCs (p<0.05). Inflammatory cell markers CD66b and CD68 also exhibited significant cohort differences (p<0.05). Exploratory analyses revealed a significant relationship between tumour immunity factors, geographic locality-specific prognosis, and postchemotherapy outcomes.Conclusions Analyses of >1600 GCs suggest that Asian and non-Asian GCs exhibit distinct tumour immunity signatures related to T-cell function. These differences may influence geographical differences in clinical outcome, and the design of future trials particularly in immuno-oncology.