An integrated bioinformatic investigation of mitochondrial energy metabolism genes in colon adenocarcinoma followed by preliminary validation of CPT2 in tumor immune infiltration

Abstract

BackgroundThe prognosis for colon adenocarcinoma (COAD) today remains poor. Changes in mitochondria-related genes and metabolic reprogramming are related to tumor growth, metastasis, and immune evasion and are key factors in tumor genesis and development.MethodsTCGA database was used to analyze the differentially expressed mitochondrial energy metabolism pathway-related genes (MMRGs) in COAD patients, and the mutation of MMRG in tumor cells, the biological processes involved, and the correlation with tumor immunity were also analyzed. Then, MMRG and MMRG-related genes were used to divide COAD patients into different subtypes, and immunocorrelation analysis and survival analysis were performed. Finally, univariate regression analysis and LASSO regression analysis were used to construct a prognostic risk model for COAD patients, which was verified by the GEO database and evaluated by Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curves, and the correlation between the risk model and immunity and clinical subtypes based on MMRG was analyzed.ResultsIn this study, the MMRG patterns and tumor immune microenvironment characteristics in COAD patients were systematically evaluated by clustering the expression of 188 MMRGs. We identified two subtypes of COAD with different clinical and immunological characteristics. Eight of the 28 differentially expressed MMRG genes were used to construct risk scores. ROC and K-M curves suggested that the risk model could well predict the prognosis of COAD patients, and the risk model was related to immune cell infiltration and immune function.ConclusionsThe two COAD subtypes identified by MMRG are helpful for the clinical differentiation of patients with different prognoses and tumor progressions, and the risk score can assist the clinical evaluation of patient prognosis. Our results suggest that CPT2 contributes to the recruitment and regulation of neutrophils in COAD. CPT2 may act as a valuable biomarker for COAD immunotherapy.

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

“…LDHA, ALDH3B1, and ALDH3A1 are all connected to the genesis and development of various cancers and play a role in mitochondrial energy metabolism. Hepatocellular carcinoma exhibits downregulation of the ATP synthesis-related gene alcohol dehydrogenase 6 (ADH6), which is a key prognostic indicator for pancreatic cancer ( Liao et al, 2017 ; Liu et al, 2020 ; Cao et al, 2022 ). These researches imply that the genes utilized to build risk models are tumor-related.…”