Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancer

The aberrant expression of RNA binding proteins (RBPs) is linked to various diseases, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the single-cell landscape of RBPs in CESC remains unclear. We analyzed single-cell data from 2 HPV + and 2 HPV- CESC samples to assess cell subtype composition and differential gene expression. Meanwhile, based on 2,141 reported RBPs, the expression patterns of different cell type-specific RBPs were further investigated. SUVA software was used to perform differential alternative splicing analysis on the TCGA CESC data. Finally, we did a lot of follow-up work and immunohistochemical studies to understand the true expression of RBP and its correlation with CESC prognosis. We observed a significant increase in the proportion of epithelial cells in the HPV + sample. The expression of RBP exhibited heterogeneity between HPV + and HPV- samples, with epithelial cells demonstrating the most diverse composition of RBP-expressing cell clusters. Results indicated that RNA splicing events were strongly associated with CESC progression. Covariation analysis identified 4 RBPs (CSTB, TIPARP, NDRG1, and NDRG2) correlated with 25 RNA alternative splicing events. Immunohistochemical experiments revealed that TIPARP expression was down-regulated in HPV + cervical cancer(p = 0.033). And the prognostic model that includes all RBPs, stage, and treatments may has have certain practical guiding significance for patients with CESC. Our study indicates that RBPs display specific expression patterns across HPV + and HPV- CESC. The regulatory checkpoints of these RBPs may serve as potential markers and therapeutic targets for the detection of HPV + CESC.