» Articles » PMID: 36814901

Comprehensive Analysis Reveals Signal and Molecular Mechanism of Mitochondrial Energy Metabolism Pathway in Pancreatic Cancer

Overview
Journal Front Genet
Date 2023 Feb 23
PMID 36814901
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Bioinformatics analysis of mitochondrial metabolism-related genes demonstrates their importance in renal cell carcinoma.

Ahmadi M, Motallebinezhad M, Mousavi P, Miladipour A, Fooladgar S, Ghafouri-Fard S Discov Oncol. 2025; 16(1):28.

PMID: 39789365 PMC: 11717778. DOI: 10.1007/s12672-025-01780-4.


Establishment of a prognostic model for pancreatic cancer based on mitochondrial metabolism related genes.

Ba Q, Wang X, Lu Y Discov Oncol. 2024; 15(1):376.

PMID: 39196457 PMC: 11358576. DOI: 10.1007/s12672-024-01255-y.


A novel mitochondrial metabolism-related gene signature for predicting the prognosis of oesophageal squamous cell carcinoma.

Lin W, Ye C, Sun L, Chen Z, Qu C, Zhu M Aging (Albany NY). 2024; 16(11):9649-9679.

PMID: 38843392 PMC: 11210263. DOI: 10.18632/aging.205892.


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

Chi H, Su L, Yan Y, Gu X, Su K, Li H Front Immunol. 2024; 15:1375143.

PMID: 38510247 PMC: 10953916. DOI: 10.3389/fimmu.2024.1375143.


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

Dominguez-Zorita S, Cuezva J Cancers (Basel). 2023; 15(15).

PMID: 37568591 PMC: 10417293. DOI: 10.3390/cancers15153775.

References
1.
Mariathasan S, Turley S, Nickles D, Castiglioni A, Yuen K, Wang Y . TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693):544-548. PMC: 6028240. DOI: 10.1038/nature25501. View

2.
Egan G, Khan D, Lee J, Mirali S, Zhang L, Schimmer A . Mitochondrial and Metabolic Pathways Regulate Nuclear Gene Expression to Control Differentiation, Stem Cell Function, and Immune Response in Leukemia. Cancer Discov. 2021; 11(5):1052-1066. DOI: 10.1158/2159-8290.CD-20-1227. View

3.
Samson J, Ravindran Menon D, Smith D, Baird E, Kitano T, Gao D . Clinical implications of ALDH1A1 and ALDH1A3 mRNA expression in melanoma subtypes. Chem Biol Interact. 2019; 314:108822. PMC: 6916670. DOI: 10.1016/j.cbi.2019.108822. View

4.
Peng M, Yin N, Chhangawala S, Xu K, Leslie C, Li M . Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science. 2016; 354(6311):481-484. PMC: 5539971. DOI: 10.1126/science.aaf6284. View

5.
Guerra F, Arbini A, Moro L . Mitochondria and cancer chemoresistance. Biochim Biophys Acta Bioenerg. 2017; 1858(8):686-699. DOI: 10.1016/j.bbabio.2017.01.012. View