Application of Prognostic Model based on Histone Phosphorylation Modification Gene in Lung Adenocarcinoma

Background : The incidence rate of lung adenocarcinoma (LUAD) is gradually increasing and the prognosis is poor. Recent studies have reported that histone phosphorylation plays an important role in the occurrence and development of tumors; however, the role of histone phosphorylation in LUAD remains unclear. Methods To investigate the role of histone phosphorylation in LUAD regulation, we first curated data on 42 genes related to this process from the published literature. This data served as the foundation for our subsequent analyses. Next,we downloaded expression data for LUAD patients from The Cancer Genome Atlas (TCGA) public database. We employed differential expression analysis (FDR < 0.05, |logFC| > 0.5) to identify genes exhibiting significant differences in expression between LUAD tissues and normal controls. This analysis yielded a set of differentially expressed genes (DEGs). From the identified DEGs, we utilized univariate Cox analysis to select 11 genes with prognostic potential. These genes were then subjected to least absolute shrinkage and selection operator regression（LASSO）analysis for the construction of a prognostic model. LUAD patients within the TCGA cohort were categorized into high- and low-risk groups based on a predefined optimal median value derived from the prognostic model. The accuracy and generalizability of the model were subsequently evaluated using data from three independent Gene Expression Omnibus（GEO） datasets. We conducted a comprehensive comparison between the high- and low-risk groups defined by the prognostic model. This comparison encompassed analyses of prognosis, clinical relevance, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of DEGs, tumor mutational burden (TMB), and immune cell infiltration. Furthermore, we employed the "estimate" package to calculate and compare the immune score, stromal score, and tumor purity across the different risk groups. Finally, to validate the expression of PBK in LUAD cell lines. Results By constructing a 6-gene prognostic model using LASSO, LUAD patients in the TCGA database were divided into high-risk and low-risk groups. Through comparison, it was found that the high-risk and low-risk groups showed significant differences in survival, immune cell infiltration, TMB, immunotherapy, and other aspects. Univariate and multivariate Cox regression analysis showed that risk score can be used as an independent prognostic factor for LUAD. Conclusion The present study is the first to use histone phosphorylation genes for the reliable prognosis of LUAD in patients. The constructed prognostic model can significantly distinguish high-risk and low-risk populations, predict the prognosis of LUAD patients, TMB, and may also guide future immunotherapy interventions for these patients.