Identification of Biomarkers for Cervical Cancer Radiotherapy Sensitivity and Survival Prognosis

Introduction: Radiotherapy resistance leads to treatment failure and disease progression in patients with cervical cancer. This study aims to elucidate the molecular underpinnings of radiotherapy response in cervical cancer by identifying radiotherapy sensitivity genes (RSGs). Methods: We utilized two GEO expression profiling datasets (GSE3578 and GSE6213) comprising cervical cancer biopsy samples taken before and during radiotherapy to identify differentially expressed genes (DEGs) using the RankProd meta-analysis approach. Subsequent analysis was conducted using data from the TCGA-CESE project to further determine the RSGs and investigate their associations with survival prognosis, immune cell infiltration, and drug sensitivities. The differential expressions of the candidate RSGs were validated in an independent set of cervical cancer patients by qPCRs. Results: A total of 518 DEGs were identified, with 305 genes upregulated and 213 genes down-regulated during radiotherapy. Six key RSGs were identified as significantly associated with radiotherapy response. Cox regression analysis revealed that upregulations of IL1RAP and GPR15 were associated with an increased risk of poor survival prognosis. Functional enrichment analysis highlighted the involvement of these genes in critical biological processes such as cytokine signaling and immune regulation. Correlation analyses demonstrated significant associations between RSG expressions and M2 macrophage and gamma delta T cell abundances in tumor microenvironment, as well as drug sensitivities. The expression of IL1RAP was significantly higher in the complete response group, supporting the bioinformatic finding. Conclusion: Our findings on RSGs could potentially serve as potential biomarkers for predicting radiotherapy response and as therapeutic targets to enhance the efficacy of radiotherapy.