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

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Aberrant expression of RNA binding proteins (RBPs) is implicated in various diseases.
• The single-cell landscape of RBPs in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is not well understood.
• Human papillomavirus (HPV) status significantly impacts CESC development and progression.

Purpose of the Study:

• To investigate the single-cell expression patterns of RBPs in HPV-positive and HPV-negative CESC.
• To identify RBPs and RNA alternative splicing events associated with CESC progression.
• To evaluate the prognostic significance of RBPs in CESC.

Main Methods:

• Single-cell RNA sequencing analysis of CESC samples.
• Differential gene expression and alternative splicing analysis using SUVA software.
• Immunohistochemical validation of RBP expression and correlation with patient prognosis.

Main Results:

• HPV-positive CESC samples showed an increased proportion of epithelial cells.
• RBP expression was heterogeneous between HPV-positive and HPV-negative CESC, with epithelial cells exhibiting diverse RBP clusters.
• Four RBPs (CSTB, TIPARP, NDRG1, NDRG2) were correlated with 25 RNA alternative splicing events; TIPARP was downregulated in HPV-positive CESC.
• A prognostic model incorporating RBPs, stage, and treatment showed potential clinical utility.

Conclusions:

• RBPs exhibit distinct expression patterns in HPV-positive versus HPV-negative CESC.
• RNA splicing events are significantly associated with CESC progression.
• RBPs represent potential biomarkers and therapeutic targets for HPV-positive CESC detection and treatment.