Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas

作者：Suling J. Lin, Johann A. Gagnon-Bartsch, Iain Beehuat Tan, Sophie Earle, Louise Ruff, Katherine Jane Pettinger, Bauke Ylstra, Nicole C.T. van Grieken, Sun Young Rha, Hyun Cheol Chung, Ju‐Seog Lee, Jae‐Ho Cheong, Sung Hoon Noh, Toru Aoyama, Yohei Miyagi, Akira Tsuburaya, Takaki Yoshikawa, Jaffer A. Ajani, Alex Boussioutas, Khay Guan Yeoh, Wei Peng Yong, Jimmy Bok Yan So, Jeeyun Lee, Won Ki Kang, Sung Hoon Kim, Yoichi Kameda, Tomio Arai, Axel zur Hausen, Terence Paul Speed, Heike Irmgard Grabsch, Patrick B. O. Tan · 发表于：Gut · 年份：2014 · DOI：10.1136/gutjnl-2014-308252 · 被引用次数：236 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Gastric Cancer Management and Outcomes

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 relatio...