生物信息学和实验方法揭示了关键线粒体代谢相关基因在宫颈癌中的潜在预后和免疫作用。
Bioinformatics and experimental approach reveal potential prognostic and immunological roles of key mitochondrial metabolism-related genes in cervical cancer.
作者信息
Huang Qing, Xu Yang-Feng, Li Hui-Ping, Zhang Ting
机构信息
Gynecology Department, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China.
Orthopedics Department, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China.
出版信息
Front Oncol. 2025 Mar 17;15:1522910. doi: 10.3389/fonc.2025.1522910. eCollection 2025.
BACKGROUND
Metabolic remodeling is the hallmark of cancer. In recent years, mitochondrial metabolism (MM) has been considered essential in tumorigenesis and cancer progression. Understanding the role of MM in cervical cancer (CC) can provide insights into disease progression and potential therapeutic targets.
METHODS
Clinical data of CC patients was downloaded from the UCSC Xena dataset, and differentially expressed genes (DEGs) were identified between tumor and normal samples. MM-related genes (MMRGs) were screened from the MSigDB database. DEGs and MMRGs were then intersected to identify differentially expressed MMRGs. A prognostic risk model was constructed based on these intersecting genes through Cox regression analysis, and its association with the tumor microenvironment and immune checkpoint-related genes was evaluated. Hub genes' expression was evaluated in cells through qRT-PCR. Additionally, drug sensitivity analysis was conducted to explore potential therapeutic drugs.
RESULTS
We identified 259 overlapping genes between DEGs and MMRGs, with 55 being prognosis-related. Two molecular clusters were revealed, with C1 exhibiting poorer prognosis. A prognostic risk model comprising five genes (BDH1, MIR210, MSMO1, POLA1, and STARD3NL) was established, showing significant associations with survival outcomes of CC patients. Functional enrichment analysis revealed that DEGs between high- and low-risk groups were tightly associated with the immune system. Analysis of the immune microenvironment showed significant differences between different risk groups, with higher immune and ESTIMATE scores observed in the low-risk group. Additionally, expression levels of immune checkpoint-related genes were significantly correlated with the risk score. Drug sensitivity analysis identified potential therapeutic agents correlated with the expression of the five prognostic genes.
CONCLUSION
Our findings underscore the importance of MM in CC progression and provide potential therapeutic targets for CC.
背景
代谢重塑是癌症的标志。近年来，线粒体代谢（MM）被认为在肿瘤发生和癌症进展中至关重要。了解MM在宫颈癌（CC）中的作用有助于深入了解疾病进展及潜在治疗靶点。
方法
从UCSC Xena数据集中下载CC患者的临床数据，确定肿瘤样本与正常样本之间的差异表达基因（DEG）。从MSigDB数据库中筛选MM相关基因（MMRG）。然后将DEG和MMRG进行交集分析，以鉴定差异表达的MMRG。通过Cox回归分析基于这些交集基因构建预后风险模型，并评估其与肿瘤微环境和免疫检查点相关基因的关联。通过qRT-PCR评估细胞中枢纽基因的表达。此外，进行药物敏感性分析以探索潜在的治疗药物。
结果
我们在DEG和MMRG之间鉴定出259个重叠基因，其中55个与预后相关。揭示了两个分子簇，C1的预后较差。建立了一个包含五个基因（BDH1、MIR210、MSMO1、POLA1和STARD3NL）的预后风险模型，该模型与CC患者的生存结果显著相关。功能富集分析表明，高风险组和低风险组之间的DEG与免疫系统密切相关。免疫微环境分析显示不同风险组之间存在显著差异，低风险组的免疫和ESTIMATE评分较高。此外，免疫检查点相关基因的表达水平与风险评分显著相关。药物敏感性分析确定了与五个预后基因表达相关的潜在治疗药物。
结论
我们的研究结果强调了MM在CC进展中的重要性，并为CC提供了潜在的治疗靶点。
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