Comprehensive analysis reveals signal and molecular mechanism of mitochondrial energy metabolism pathway in pancreatic cancer

Abstract

Pancreatic cancer (PAAD) is one of the most malignant tumors with the worst prognosis. The abnormalities in the mitochondrial energy metabolism pathway are intimately correlated with the occurrence and progression of cancer. For the diagnosis and treatment of pancreatic cancer, abnormal genes in the mitochondrial energy metabolism system may offer new targets and biomarkers. In this study, we compared the dysregulated mitochondrial energy metabolism-associated pathways in PAAD based on pancreatic cancer samples in the Cancer Genome Atlas (TCGA) database and normal pancreas samples from the Genotype Tissue Expression project (GTEx) database. Then identified 32 core genes of mitochondrial energy metabolism pathway-related genes (MMRG) were based on the gene set enrichment analysis (GSEA). We found most of these genes were altered among different clinical characteristic groups, and showed significant prognostic value and association with immune infiltration, suggesting critical roles of MMRG involve tumor genesis of PAAD. Therefore, we constructed a four-gene (LDHA, ALDH3B1, ALDH3A1, and ADH6) prognostic biomarker after eliminating redundant factors, and confirming its efficiency and independence. Further analysis indicated the potential therapeutic compounds based on the mitochondrial energy metabolism-associated prognostic biomarker. All of the above analyses dissected the critical role of mitochondrial energy metabolism signaling in pancreatic cancer and gave a better understanding of the clinical intervention of PAAD.

Illuminating the immunological landscape: mitochondrial gene defects in pancreatic cancer through a multiomics lens

“…In the context of pancreatic cancer, particular mitochondrial gene defects significantly influence tumor biology ( 17 , 18 , 61 , 62 ). Mutations in genes such as MT-ND4 (mitochondrial NADH dehydrogenase subunit 4) have been implicated in compromising the mitochondrial electron transport chain, leading to increased intracellular oxidative stress and destabilized energy metabolism ( 54 , 63 ).…”

The Mitochondrial ATP Synthase/IF1 Axis in Cancer Progression: Targets for Therapeutic Intervention

“…The relevance of a low BEC index in predicting a poor prognosis for patients bearing different types of carcinomas (breast, colon, lung, melanoma, ovarian, gallbladder) and leukemias has been extensively documented [16,35,39,115,[142][143][144][145][146][147][148][149][150]. Furthermore, the BEC index significantly correlates with migration speed and in predicting drug responses across the NCI-60 cell line panel [151], as well as in predicting the response to different targeted therapies in preclinical mouse models bearing different human carcinomas [20,39,51,[60][61][62]120,152,153].…”