Prognostic alternative splicing and multi-omics characteristics reveal FTCD is a potential target of hepatocellular...

This research aimed to identify alternative splicing (AS) variants in hepatocellular carcinoma (HCC) and assess their prognostic biomarker potential. We analyzed genome-wide prognostic-associated AS events to pinpoint specific genes that could predict HCC patient outcomes and serve as therapeutic targets.

Analyzing 343 liver cancer samples from The Cancer Genome Atlas (TCGA) via RNA-seq, we evaluated the impact of seven AS patterns on HCC. We constructed a prognostic prediction model using Cox proportional hazards regression and developed a splicing network by correlating survival-associated AS events with splicing factor expression. Notably, we investigated Formiminotransferase cyclodeaminase (FTCD) gene for its role in liver cancer cell proliferation and pathway mechanisms in mice and cell models.

We discovered 3164 survival-associated AS events, with the top 20 mostly indicating poor prognosis. Our prognostic model, integrating various AS patterns, demonstrated robust performance in stratifying HCC risk (AUC = 0.830). Splicing network analysis highlighted significant correlations between splicing factors and AS events. Lower expression of FTCD, associated with adverse HCC outcomes, was found to regulate cell proliferation via the PI3K/AKT/mTOR pathway.

This study offers a prognostic prediction model for HCC patient risk stratification, identifying the FTCD gene as a crucial prognostic marker and therapeutic target. This highlights FTCD's potential impact on HCC clinical diagnosis and treatment strategies.