Systematic profiling of alternative splicing of ZNF family in Colorectal cancer

Abstract

Backgrounds: Colorectal cancer (CRC) is a global health issue that requires innovative prognostic signatures to improve patient outcomes. Alternative splicing (AS) of RNA is a crucial modification process involved in cancer progression, and zinc finger proteins (ZNFs), the largest family of DNA binding proteins, have been implicated in various aspects of cancer development. However, the role of ZNF AS events in cancer remains poorly understood. Methods: To address this, we investigated the relationship between ZNF AS and CRC development using clinical samples and bioinformatics approaches to identify a prognostic signature. Results: We identified 227 differentially expressed genes (DEGs) and 98 survival-related genes among ZNFs. We also identified 29 differentially expressed AS (DEAS) events and 93 survival-related AS events in CRC patients. Using these results, we developed a thirteen-AS signature that showed excellent predictive ability, with a 3-year area under the receiver operating characteristic (ROC) curve (AUC) value of 0.80, outperforming the commonly used tumor-node-metastasis (TNM) staging-based model (AUC = 0.73). Gene Set Enrichment Analysis (GSEA) showed that the risk score of our model was associated with various cancer-related pathways, including PI3K AKT MTOR, CELL CYCLE, APOPTOSIS, and more. We also validated our findings through qPCR and explored the correlations between splicing factors (SFs) and DEAS events. Conclusions: Our study provides new insights into the role of ZNFs in cancer and highlights their potential as prognostic biomarkers for CRC progression.