FAM gene expression predicts prognosis and immune microenvironment in microsatellite-stable colorectal cancer

Abstract

Background: The FAM (family with sequence similarity) gene family, implicated in various malignancies, remains underexplored in microsatellite-stable (MSS) colorectal cancer (CRC). MSS CRC represents the majority of CRC cases and lacks reliable prognostic biomarkers as well as effective immunotherapeutic strategies.

Methods: Transcriptome profiles and matched clinical data from The Cancer Genome Atlas-COADREAD cohort were used as a training set, while GSE29623 and GSE39582 served as independent validation cohorts. A prognostic signature (FAM gene Family-associated expression scoring (FAMscore)) was constructed based on FAM family genes using Multivariate-Cox regression. Associations between FAMscore, survival outcomes, tumor immune microenvironment features, and predicted drug sensitivity were explored through computational analyses.

Results: The FAMscore stratified MSS CRC patients into high- and low-risk groups with significantly different (P ≤ 0.05) overall survival (OS) in the training cohort and consistent trends in validation datasets. A high FAMscore was associated with an immunosuppressive tumor immune microenvironment, characterized by increased regulatory T cells and M2 macrophages. Exploratory analyses suggested differential predicted sensitivity to selected targeted agents.

Conclusions: FAMscore is associated with prognosis and immune landscape features in MSS CRC. These findings are exploratory and hypothesis-generating, and further experimental and prospective validation is required.

Keywords

MSS colorectal cancer / FAM gene family / prognostic model / tumor immune microenvironment

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