Signature and Molecular Mechanism of Mitochondrial Energy Metabolism Pathway-Related Genes in Lung Adenocarcinoma.

Abstract

Objective The mitochondrial energy metabolic pathway (MEMP) is the primary energy metabolism of tumor cells, and its disruption may promote cancer emergence, spreading, and immune escape. However, there is a lack of studies to determine the relationship between relevant functional mechanisms and lung adenocarcinoma (LUAD) prognosis. Methods Gene set enrichment analysis (GSEA) was employed to determine MEMP pathway-related genes. Then, a prognostic model was created using the MEMP key genes that were found by LASSO-Cox regression analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided the training and validation sets. Furthermore, the infiltration of immune cells was examined by ssGSEA. Finally, a screening of candidate therapeutic compounds for LUAD patients was performed using DrugBank, Protein Data Bank (PDB), and AutoDock Vina databases. Results First, 266 MEMP pathway-related genes that exhibited aberrant activity in tumors were identified. Then, 19 MEMP key genes were used to build a prognostic model, which can successfully predict the survival rates of LUAD patients after 1, 3, and 5 years, respectively. The Kaplan-Meier curve showed that patients in the high-risk group had considerably lower survival outcomes than those in the low-risk group. Furthermore, it was discovered that the high-risk group had the majority of activated T cells, while the low-risk group tended to have more other activated immune cells. The majority of immunological checkpoints expressed themselves more strongly in the high-risk group as well. Finally, 11 prospective medication small molecules were obtained from the projected potential therapeutic drugs, with DB0980 being regarded as the most promising of them for the treatment of LUAD. Conclusion This current study developed reliable prognostic signature, called MEMP score, which provides new guidance for prognostic assessment, immunotherapy, and drug development in LUAD. Thereby, DB0980 appears to be the most likely approach for the treatment of LUAD.