論文

査読有り 国際誌
2015年11月

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

Gut
  • Suling J Lin
  • Johann A Gagnon-Bartsch
  • Iain Beehuat Tan
  • Sophie Earle
  • Louise Ruff
  • Katherine Pettinger
  • Bauke Ylstra
  • Nicole 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 So
  • Jeeyun Lee
  • Won Ki Kang
  • Sung Kim
  • Yoichi Kameda
  • Tomio Arai
  • Axel Zur Hausen
  • Terence P Speed
  • Heike I Grabsch
  • Patrick Tan
  • 全て表示

64
11
開始ページ
1721
終了ページ
31
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1136/gutjnl-2014-308252

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.

リンク情報
DOI
https://doi.org/10.1136/gutjnl-2014-308252
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25385008
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680172
ID情報
  • DOI : 10.1136/gutjnl-2014-308252
  • PubMed ID : 25385008
  • PubMed Central 記事ID : PMC4680172

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