Heterogeneity of MSI-H gastric cancer identifies a subtype with worse survival.

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. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.