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

Authors
 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 
Citation
 GUT, Vol.64(11) : 1721-1731, 2015 
Journal Title
GUT
ISSN
 0017-5749 
Issue Date
2015
MeSH
Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics* ; Adenocarcinoma/immunology* ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/genetics ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics* ; Stomach Neoplasms/immunology* ; Transcriptome* ; Treatment Outcome ; Young Adult
Keywords
GASTRIC CANCER ; GENE EXPRESSION ; IMMUNOLOGY ; MOLECULAR MECHANISMS ; MOLECULAR PATHOLOGY
Abstract
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.
Full Text
http://gut.bmj.com/content/64/11/1721.long
DOI
10.1136/gutjnl-2014-308252
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141621
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