SF3A2: a promising therapeutic target and predictive biomarker for immunotherapy in colorectal cancer

Colorectal cancer (CRC) is one of the most prevalent malignancies globally and poses a substantial threat to human health. The current understanding of the biological significance of Splicing Factor 3a Subunit 2(SF3A2) in CRC remains limited. In this study, the upregulation of SF3A2 in CRC was identified through TMT-based quantitative proteomic screening of surgically resected paired primary cancer and normal epithelial tissues. Patients with elevated SF3A2 expression exhibited reduced survival compared to those with lower expression levels. Knockdown of SF3A2 significantly decreased cell proliferation, migration, and invasive properties both in vivo and in vitro. Bioinformatics enrichment analysis revealed that SF3A2 was involved in alternative splicing and functioned as an oncogene by modulating the expression of genes associated with critical tumorigenesis pathways and functions. Furthermore, immune infiltration analysis using multiple algorithms (including TIMER, EPIC, QUANTISEQ, and MCPCOUNTER) indicated an inverse relationship between SF3A2 expression levels and the presence of various immune cell types. Concurrently, predictions derived from the TIDE algorithm corroborated that patients exhibiting elevated SF3A2 expression were likely to experience a diminished response to immunotherapy. In summary, SF3A2 emerged as a promising therapeutic target for CRC and served as a novel biomarker for forecasting responses to immunotherapeutic interventions.