Global Proteomic Analysis of Colorectal Cancers Stratified by Microsatellite Instability Subtype Reveals Protein Differences

Label-free bottom-up proteomics of 122 colorectal tumor and matched normal samples from 61 patients shows MSS CRC proteomes are significantly distinct from three MSI-high Lynch-related subtypes.

• Why it matters: Genetic alterations in Lynch syndrome are known, but proteomic changes have been poorly characterized due to scarce primary tissue and lack of suitable in vitro models.
• What they did: Using specimens from the Ohio Colorectal Cancer Prevention Initiative, the study profiled 7,352 proteins across Lynch syndrome, double somatic MMR mutation, MLH1 hypermethylation, and MSS CRC, then performed hierarchical clustering and dysregulation analyses.
• The result: Among 1,607 dysregulated proteins in CRC, 648 were specific to Lynch syndrome and 260 were dysregulated across all four subtypes, enabling subtype-resolved protein signatures.

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