Recognition of driver genes with potential prognostic implications in lung adenocarcinoma based on H3K79me2

Lung adenocarcinoma is a malignancy with a low overall survival and a poor prognosis. Studies have shown that lung adenocarcinoma progression relates to locus-specific/global changes in histone modifications. To explore the relationship between histone modification and gene expression changes, we focused on 11 histone modifications and quantitatively analyzed their influences on gene expression. We found that, among the studied histone modifications, H3K79me2 displayed the greatest impact on gene expression regulation. Based on the Shannon entropy, 867 genes with differential H3K79me2 levels during tumorigenesis were identified. Enrichment analyses showed that these genes were involved in 16 common cancer pathways and 11 tumors and were target-regulated by trans-regulatory elements, such as Tp53 and WT1. Then, an open-source computational framework was presented (https://github.com/zlq-imu/Identification-of-potential-LUND-driver-genes). Twelve potential driver genes were extracted from the genes with differential H3K79me2 levels during tumorigenesis. The expression levels of these potential driver genes were significantly increased/decreased in tumor cells, as assayed by RT–qPCR. A risk score model comprising these driver genes was further constructed, and this model was strongly negatively associated with the overall survival of patients in different datasets. The proportional hazards assumption and outlier test indicated that this model could robustly distinguish patients with different survival rates. Immune analyses and responses to immunotherapeutic and chemotherapeutic agents showed that patients in the high and low-risk groups may have distinct tendencies for clinical selection. Finally, the regions with clear H3K79me2 signal changes on these driver genes were accurately identified. Our research may offer potential molecular biomarkers for lung adenocarcinoma treatment.