Multi-Omics Integration Identifies Critical Molecular Drivers and Alternative Splicing Events in Small Cell Lung Cancer

Here, we conducted an integrated multi-omics analysis of treatment-naïve human SCLC tissues along with paired adjacent tissues (NAT, n = 12), including transcriptomic, proteomic, phosphoproteomic, and glycoproteomic profiling to identify novel prognostic markers and therapeutic targets. Integration of these datasets revealed significant enrichment of RNA splicing pathway in SCLC.

We systematically characterized aberrant alternative splicing events (AASEs), identifying 6,972 events with exon skipping representing the most prevalent type. These AASEs were regulated by RNA-binding proteins and predominantly enriched in pathways related to tumor proliferation and metastasis. We further identified four splicing-related proteins (THOC1, MAGOHB, RBM8A, and TXNL4A) that were markedly overexpressed in SCLC, correlated with proliferation, and predicted poor prognosis.