A histone acetylation-based predictive model for immunotherapy response and combinatorial targeting in cervical cancer

Histone acetylation, a fundamental component of epigenetic modification, plays a pivotal role in the progression, treatment, and prognosis of numerous cancers. In this study, we systematically investigated, for the first time, the clinical value of histone acetylation (HAT) modification in the prognostic assessment of cervical cancer. Utilizing the GSE44001 and The Cancer Genome Atlas-CESC databases, a HAT-associated prognostic model comprising 7 pivotal genes was formulated through Lasso-Cox regression analysis. The integration of multiple bioinformatics algorithms (including Cibersort, ESTIMATE, ssGSEA, and TIDE) has enabled the profound delineation of immune microenvironmental characteristics among disparate risk groups. Utilizing molecular docking technology, we conducted a screening process that identified 2 potential target drugs. The prognostic model's predictive efficacy was successfully validated in an independent cohort. The analysis has revealed that the high-risk group exhibits a pronounced immunosuppressive phenotype. The study identified 2 additional factors that contribute to the prognosis of cervical cancer: CPE and PGK1. These factors have been shown to be significantly associated with poor clinical outcomes. In addition, we have identified 2 drugs that may target CPE and PGK1, namely Z-LLNle-CHO and OSU-03-012. The discovery of these drugs has opened up a new potential pathway for overcoming resistance to immunotherapy. This study addresses a significant research gap concerning HAT in the prognostic assessment of cervical cancer. Furthermore, it offers a crucial molecular basis for clinical decisions regarding individualized therapeutic interventions.