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Updated: Dec 26, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Heterogeneity of MSI-H gastric cancer identifies a subtype with worse survival
Yanmei Yang1, Zhong Shi2, Rui Bai3
1Key Laboratory of Reproductive and Genetics, Ministry of Education, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China yangyanmei@zju.edu.cn wxhu@zju.edu.cn.
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.
