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Cancer genetics
Original research
Heterogeneity of MSI-H gastric cancer identifies a subtype with worse survival
  1. Yanmei Yang1,
  2. Zhong Shi2,
  3. Rui Bai3,
  4. Wangxiong Hu3
  1. 1 Key Laboratory of Reproductive and Genetics, Ministry of Education, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
  2. 2 Department of Medical Oncology, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
  3. 3 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  1. Correspondence to Yanmei Yang; yangyanmei{at}zju.edu.cn; Dr. Wangxiong Hu; wxhu{at}zju.edu.cn

Abstract

Background Microsatellite instability-high (MSI-H) tumour patients generally have a better prognosis than microsatellite-stable (MSS) ones due to the large number of non-synonymous mutations. However, an increasing number of studies have revealed that less than half of MSI-H patients gain survival benefits or symptom alleviation from immune checkpoint-blockade treatment. Thus, an in-depth inspection of heterogeneous MSI-H tumours is urgently required.

Methods Here, we used non-negative matrix factorisation (non-NMF)-based consensus clustering to define stomach adenocarcinoma (STAD) MSI-H subtypes in samples from The Cancer Genome Atlas and an Asian cohort, GSE62254.

Results MSI-H STAD samples are basically clustered into two subgroups (MSI-H1 and MSI-H2). Further examination of the immune landscape showed that immune suppression factors were enriched in the MSI-H1 subgroup, which may be associated with the poor prognosis in this subgroup.

Conclusions Our results illustrate the genetic heterogeneity within MSI-H STADs, with important implications for cancer patient risk stratification, prognosis and treatment.

  • immune checkpoint blockade
  • microsatellite instability-high
  • stomach adenocarcinoma
  • subtyping

https://doi.org/10.1136/jmedgenet-2019-106609

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    Footnotes

    • Contributors Conception and design: WH. Provision of study materials or patients: WH. Collection and assembly of data: Y-MY, RB, WH. Data analysis and interpretation: Y-MY, ZS, WH.

    • Funding This work was supported by the National Natural Science Foundation of China (grant number 81802883 and 81602583) and Fundamental Research Funds for the Central Universities (grant number 2018FZA7012).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available in a public, open access repository. The datasets generated and/or analysed during the current study are available in the TCGA repository, https://cancergenome.nih.gov/.