Exploring the role of disulfidptosis-related signatures in immune microenvironment, prognosis and therapeutic strategies of cervical cancer

Background: Cervical cancer is characterized by a complex immunosuppressive tumor microenvironment (TME). Disulfidptosis is a recently identified form of programmed cell death that has emerged as a crucial factor in tumorigenesis. However, the research on the specific involvement of disulfidptosis within the TME is still in its early stages. Methods: Under glucose starvation, SiHa and HeLa cells underwent experiments employing diverse cell death inhibitors and SLC7A11 knockdown to observe their impact on cell survival. TCGA-CESC cohort was subjected to consensus clustering for disulfidptosis-related clusters. Prognosis, function, immune infiltration, and differentially expressed genes (DEGs) evaluations among clusters were compared. A prognostic model based on DEGs and disulfidptosis regulator genes (DRGs) was constructed and internally and externally validated. The correlation between YWHAG and clinicopathological characteristics in cervical cancer patients was investigated at both the mRNA and protein levels. Proliferation and migration assays were performed to uncover the roles of YWHAG in cervical cancer. Results: Experimental validation confirmed disulfidptosis in cervical cancer cell lines. Cervical cancer patients were classified into three clusters based on DRGs, showing notably improved prognosis and increased immune infiltration in cluster B. The developed disulfidptosis-related prognostic model effectively stratified patients into high- and low-risk groups. Low-risk patients exhibited more favorable responses to immunotherapy and improved overall prognosis. Additionally, YWHAG, recognized as a tumor-promoting gene, demonstrated active roles in enhancing the growth, migration, and invasion of cervical cancer cells. Conclusion: Our research proposed a prognostic model for cervical cancer, probably contributing to tumor microenvironment traits and more potent immunotherapy strategy exploration.