Drug Design, Development and Therapy (Jul 2024)
Unraveling Crucial Mitochondria-Related Genes in the Transition from Ulcerative Colitis to Colorectal Cancer
Abstract
Fanqi Wang,1,2,* Limin Xie,1,2,* Yuan Tang,1,2 Tuo Deng3 1National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Key Laboratory of Diabetes Immunology, Ministry of Education, and Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3Clinical Immunology Center, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tuo Deng, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +8613755063233, Email [email protected]: To clarify the significance of mitochondria-related differentially expressed genes (MTDEGs) in UC carcinogenesis through a bioinformatics analysis and provide potential therapeutic targets for patients with UC associated colorectal cancer.Methods: Microarray GSE37283 was utilized to investigate differentially expressed genes (DEGs) in UC and UC with neoplasia (UCN). MTDEGs were identified by intersecting DEGs with human mitochondrial genes. Utilizing LASSO and random forest analyses, we identified three crucial genes. Subsequently, using ROC curve to investigate the predictive ability of three key genes. Following, three key genes were confirmed in AOM/DSS mice model by Real-time PCR. Finally, single-sample gene set enrichment analysis (ssGSEA) was employed to explore the correlation between the hub genes and immune cells infiltration in UC carcinogenesis.Results: The three identified hub MTDEGs (HMGCS2, MAVS, RDH13) may exhibit significant diagnostic specificity in the transition from UC to UCN. Real-time PCR assay further confirmed that the expressions of HMGCS2 and RDH13 were significantly downregulated in UCN mice than that in UC mice. ssGSEA analysis revealed the hub genes were highly associated with CD56dim natural killer cells.Conclusion: RDH13, HMGCS2, and MAVS may become diagnostic indicators and potential biomarkers for UCN. Our research has the potential to enhance our understanding of the mechanisms underlying carcinogenesis in UC.Keywords: ulcerative colitis, colorectal cancer, autoimmunity diseases, mitochondria, NKT cells
