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
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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/.