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Abstract
Purpose
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.
Abbreviations
UC, ulcerative colitis; UCN, ulcerative colitis with neoplasia; DEGs, differentially expressed genes; MTDEGs, mitochondria-related differentially expressed genes; ROS, reactive oxidative species; AUC, area under the curve; TCA, the tricarboxylic acid; mtDNA, mitochondrial DNA; LASSO, the least absolute shrinkage and selection operator; HMGCS2: 3-hydroxy-3-methylglutaryl-CoA synthase 2; MAVS, mitochondrial antiviral-signaling protein; RDH13: retinol dehydrogenase 13.
Ethical Approval Statement
Our study used publicly available human data and has obtained an exemption from ethical approval by the Ethics Committee of the National Clinical Medical Research Center of The Second Xiangya Hospital, Central South University (approval number: 2024 No. M02).
Acknowledgments
We express our appreciation for the assistance rendered by the National Key Research and Development Program of China (2020YFA0803604) and the National Natural Science Foundation of China, Key Program (82130024). We express our gratitude to the GEO database for granting access to their platforms. Additionally, we acknowledge and appreciate the contributors for sharing their meaningful datasets.
Disclosure
The authors report no conflicts of interest in this work.