National 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.
Key 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.
Drug Des Devel Ther. 2024 Jul 24;18:3175-3189. doi: 10.2147/DDDT.S455098. eCollection 2024.
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.
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.
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.
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.
通过生物信息学分析，阐明与线粒体相关的差异表达基因（MTDEGs）在 UC 癌变中的意义，并为 UC 相关结直肠癌患者提供潜在的治疗靶点。
利用微阵列 GSE37283 研究 UC 和 UC 伴肿瘤（UCN）中的差异表达基因（DEGs）。通过与人类线粒体基因的交集识别 MTDEGs。利用 LASSO 和随机森林分析，我们鉴定了三个关键基因。然后，使用 ROC 曲线研究三个关键基因的预测能力。接下来，通过 Real-time PCR 验证 AOM/DSS 小鼠模型中的三个关键基因。最后，采用单样本基因集富集分析（ssGSEA）探讨核心基因与 UC 癌变中免疫细胞浸润的相关性。
三个鉴定的关键 MTDEGs（HMGCS2、MAVS、RDH13）在 UC 向 UCN 的转变中可能具有显著的诊断特异性。Real-time PCR 检测进一步证实，UCN 小鼠中 HMGCS2 和 RDH13 的表达明显低于 UC 小鼠。ssGSEA 分析表明，这些核心基因与 CD56dim 自然杀伤细胞高度相关。
RDH13、HMGCS2 和 MAVS 可能成为 UCN 的诊断指标和潜在的生物标志物。我们的研究有助于深入了解 UC 癌变的机制。
