Constructing a novel mitochondrial-related gene signature for evaluating the tumor immune microenvironment and predicting survival in stomach adenocarcinoma

Abstract

Background The incidence and mortality of gastric cancer ranks fifth and fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction and the initiation and progression of stomach cancer. However, rare prognostic models for mitochondrial-related gene risk have been built up in stomach cancer. Methods In current study, the expression and prognostic value of mitochondrial-related genes in stomach adenocarcinoma (STAD) patients were systematically analyzed to establish a mitochondrial-related risk model based on available TCGA and GEO databases. The tumor microenvironment (TME), immune cell infiltration, tumor mutation burden, and drug sensitivity of gastric adenocarcinoma patients were also investigated using R language, GraphPad Prism 8 and online databases. Results We established a mitochondrial-related risk prognostic model including NOX4, ALDH3A2, FKBP10 and MAOA and validated its predictive power. This risk model indicated that the immune cell infiltration in high-risk group was significantly different from that in the low-risk group. Besides, the risk score was closely related to TME signature genes and immune checkpoint molecules, suggesting that the immunosuppressive tumor microenvironment might lead to poor prognosis in high-risk groups. Moreover, TIDE analysis demonstrated that combined analysis of risk score and immune score, or stromal score, or microsatellite status could more effectively predict the benefit of immunotherapy in STAD patients with different stratifications. Finally, rapamycin, PD-0325901 and dasatinib were found to be more effective for patients in the high-risk group, whereas AZD7762, CEP-701 and methotrexate were predicted to be more effective for patients in the low-risk group. Conclusions Our results suggest that the mitochondrial-related risk model could be a reliable prognostic biomarker for personalized treatment of STAD patients.

New genetic insights into immunotherapy outcomes in gastric cancer via single-cell RNA sequencing and random forest model

“…The validation of our risk score as an autonomous prognostic indicator further emphasizes its utility in clinical settings [ 43 ]. This study contributes a novel, highly accurate tool for prognostic assessment, offering the potential to significantly improve patient management in gastric cancer, highlighting the transformative impact of integrating molecular and computational approaches in the fight against this formidable cancer [ 54 ].…”

miR-1182-mediated ALDH3A2 inhibition affects lipid metabolism and progression in ccRCC by activating the PI3K-AKT pathway

“…Due to the prominent prognostic relevance of ALDH3A2 in genes associated with fatty acid metabolism pathways, it was chosen as the focus of our study. This gene encodes aldehyde dehydrogenase and plays a critical role in maintaining intracellular redox balance, regulating metabolic pathways, and potentially exerting anti-tumor effects [37] , [38] , [39] . In this context, ALDH3A2 has been found to inhibit lipid accumulation in ccRCC.…”

Validation of mitochondrial biomarkers and immune dynamics in polycystic ovary syndrome

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