Evidence map›Paper›PMID 25385008›Full record

ArticleGut2015

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

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 and 21 more

Open access · hybridAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 9 pooled it
8.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

137 citing papers in PubMed, 9 syntheses or guidelines pooled it, 234 citations in OpenAlex.

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  17. Regional differences in advanced gastric cancer: exploratory analyses of the AVAGAST placebo arm.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2018
    Trial
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  19. Importance of Inclusion of Representative Populations in Pivotal Clinical Trials: Zolbetuximab as an Example.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
    Article
  20. Review

77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 16 institutions in 7 countries.

Suling J LinDepartment of Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
Johann A Gagnon-BartschDepartment of Statistics, University of California at Berkeley, Berkeley, California, USA.
Iain Beehuat TanDepartment of Medical Oncology, National Cancer Centre, Singapore, Singapore.
Sophie EarleSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Louise RuffSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Katherine PettingerSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Bauke YlstraDepartment of Pathology, Free University Medical Center Amsterdam, Amsterdam, The Netherlands.
Nicole van GriekenDepartment of Pathology, Free University Medical Center Amsterdam, Amsterdam, The Netherlands.
Sun Young RhaDepartment of Internal Medicine, Yonsei Cancer Center, Seoul, South Korea.
Hyun Cheol ChungDepartment of Internal Medicine, Yonsei Cancer Center, Seoul, South Korea.
Ju-Seog LeeDivision of Cancer Medicine, Department of Systems Biology, MD Anderson Cancer Center, Houston, Texas, USA.
Jae Ho CheongDepartment of Surgery, Yonsei University College of Medicine, Seoul, South Korea.
Sung Hoon NohDepartment of Surgery, Yonsei University College of Medicine, Seoul, South Korea.
Toru AoyamaDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan.
Yohei MiyagiMolecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Akira TsuburayaGastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
Takaki YoshikawaDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan.
Jaffer A AjaniDepartments of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, USA.
Alex BoussioutasCancer Genomics and Biochemistry Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia Department of Medicine Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Khay Guan YeohDepartment of Medicine, National University Health System, Singapore, Singapore Department of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore.
Wei Peng YongNational University Cancer Institute, Singapore, Singapore.
Jimmy SoDepartment of Surgery, National University Health System, Singapore, Singapore.
Jeeyun LeeDepartment of Medicine, Division of Haematology-Oncology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Won Ki KangDepartment of Medicine, Division of Haematology-Oncology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Sung KimDepartment of Surgery, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Yoichi KamedaDepartment of Pathology, Kanagawa Cancer Center Hospital, Yokohama, Japan.
Tomio AraiDepartment of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Axel Zur HausenDepartment of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands.
Terence P SpeedDepartment of Statistics, University of California at Berkeley, Berkeley, California, USA Bioinformatics Division, Walter and Eliza Hall Institute, Victoria, Australia Department of Mathematics and Statistics, University of Melbourne, Australia.
Heike I GrabschSection of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands.
Patrick TanDepartment of Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore.
Yonsei University · KRThe University of Texas MD Anderson Cancer Center · USUniversity of Leeds · GBGenome Institute of Singapore · SGKanagawa Cancer CenterKanagawa Prefectural Hospital Organization · JPMaastricht University · NLNational University Health System · SGUniversity of Melbourne · AUNational Cancer Centre Singapore · SGNational University Cancer Institute, Singapore · SGSamsung Medical Center · KRSungkyunkwan University · KRTokyo Metropolitan Geriatric Hospital · JPUniversity of California, Berkeley · USYokohama City University Medical Center · JP

Funding

DEVELOPMENT AND VALIDATION OF PROGNOSTIC MODEL FOR GASTRIC CANCERR01CA150229 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LEE, JU-SEOG · 2010 to 2013
$1.1M
NCI NIH HHS R01 CA150229NCI NIH HHS R01CA150229
6 · The paper itself

Abstract

objectiveDifferences 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.

designWe 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).

resultsGene 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.

conclusionsAnalyses 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.

Indexed as

TranscriptomeAdenocarcinomaAdultAgedAged, 80 and overAsian PeopleFemaleHumansMaleMiddle AgedRetrospective StudiesStomach NeoplasmsTreatment OutcomeYoung AdultGASTRIC CANCERGENE EXPRESSIONIMMUNOLOGYMOLECULAR MECHANISMSMOLECULAR PATHOLOGY

Identifiers

PMID25385008
PMCPMC4680172
OpenAlexW2150024391

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.