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PubMed · 40992503

Integrated Multiomics Analysis of Microsatellite Instability-High Colorectal Cancer Identifies a Subtype With Poor Outcome.

Gangzhi Zhang·Biting Zhou·Xiaoxian Xu·Yang Che·Wenjie Hong·Shu Zheng·Suzhan Zhang·Wangxiong Hu·Yanmei Yang
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Abstract

Up to 50% of patients with metastatic microsatellite instability-high (MSI-H) colorectal cancer (CRC) are resistant to immunotherapy and experience progression or recurrence after treatment. We integrated the genomic, epigenomic, transcriptomic, and proteomic data for 99 patients in a Chinese MSI-H CRC cohort. Proteomic profiling of primary tumors clearly classified MSI-H tumors into 2 subtypes. We found that the 2 subtypes have different mutational signatures, enriched pathways, gene fusion networks, and clinical outcomes. Notably, NCAM1 could serve as a potential biomarker for checkpoint inhibitor response in MSI-H CRC. Thus, there is an urgent need to stratify the MSI-H group into different subtypes and adopt more targeted therapies to prolong patient survival.

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HumansMicrosatellite InstabilityColorectal NeoplasmsFemaleMaleBiomarkers, TumorMiddle AgedAgedProteomicsTranscriptomeCD56 AntigenGenomicsMultiomicsNCAM1colorectal cancerdata-independent acquisitionmicrosatellite instability-highmultiomicsJournal ArticleResearch Support, Non-U.S. Gov't

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Gangzhi Zhang, Biting Zhou, Xiaoxian Xu, Yang Che, Wenjie Hong, Shu Zheng, Suzhan Zhang, Wangxiong Hu, Yanmei Yang. 2025-09-22. Integrated Multiomics Analysis of Microsatellite Instability-High Colorectal Cancer Identifies a Subtype With Poor Outcome.. https://doi.org/10.1016/j.modpat.2025.100896

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