Novel Histone Acetylation Regulators: Mediators of Tumor Microenvironment Infiltration and Prognostic Model in Cervical Cancer Patients

Background: Cervical cancer (CC) is the second most prevalent mortality rate for women’ cancer globally and the fourth most prevalent gynecological tumor. Dysregulation of histone acetylation (HA) influences the pathogenesis of cancer. However, there is a dearth of comprehensive research on HA in CC. Methods: We conducted univariate and multivariate Cox and LASSO regression analyses to assess the prognostic relevance of 36 HA-related genes identified in previous studies. A prognostic model was developed by utilizing the TCGA cohort as the training dataset and the screened HA genes. The model was subsequently validated on GSE68339 dataset. In order to confirm the accuracy of the model, Kaplan–Meier analysis and time-dependent receiver operating characteristics (ROC) were implemented. The study also investigated the associations between immune cell infiltration characteristics, immune checkpoint genes, and drug sensitivity. Lastly, the essential genes were verified through qRT-PCR and immunohistochemistry. Results: KAT2B , HDAC5 , and HDAC10 were identified as pivotal for prognosis among the 36 HA genes that were analyzed. The prognostic model classified TCGA patients into high- and low-risk groups based on risk scores, revealing significantly reduced overall survival (OS) in the high-risk group. High-risk patients demonstrated decreased immune infiltration and checkpoint gene expression. KAT2B , HDAC5 , and HDAC10 were downregulated in CC compared to normal tissues, which was correlated with poorer 5-year OS rates. qRT-PCR and immunohistochemistry confirmed reduced expression of HDAC5 and HDAC10 in clinical samples. Conclusions: We propose a prognostic model based on three HA genes that demonstrates a well predictive effect on CC patients, offering predictive value and potential application in clinical treatments.