生物信息学和实验方法揭示了宫颈癌中关键线粒体代谢相关基因的潜在预后和免疫学作用。

IF 3.5 3区 医学 Q2 ONCOLOGY
Frontiers in Oncology Pub Date : 2025-03-17 eCollection Date: 2025-01-01 DOI:10.3389/fonc.2025.1522910
Qing Huang, Yang-Feng Xu, Hui-Ping Li, Ting Zhang
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引用次数: 0

摘要

背景:代谢重塑是癌症的标志。近年来,线粒体代谢(MM)被认为是肿瘤发生和癌症进展的关键。了解MM在宫颈癌(CC)中的作用可以为疾病进展和潜在的治疗靶点提供见解。方法:从UCSC Xena数据集中下载CC患者的临床资料,鉴定肿瘤和正常样本之间的差异表达基因(DEGs)。从MSigDB数据库中筛选mm相关基因(MMRGs)。然后将DEGs和MMRGs相交以鉴定差异表达的MMRGs。通过Cox回归分析,基于这些交叉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相关性。通过qRT-PCR检测Hub基因在细胞中的表达情况。此外,还进行了药物敏感性分析,以探索潜在的治疗药物。结果:我们在DEGs和MMRGs之间鉴定了259个重叠基因,其中55个与预后相关。2个分子簇显示,C1预后较差。建立了由5个基因(BDH1、MIR210、MSMO1、POLA1和STARD3NL)组成的预后风险模型,发现与CC患者的生存结果存在显著相关性。功能富集分析显示,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5种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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bioinformatics and experimental approach reveal potential prognostic and immunological roles of key mitochondrial metabolism-related genes in cervical cancer.

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.

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来源期刊
Frontiers in Oncology
Frontiers in Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
6.20
自引率
10.60%
发文量
6641
审稿时长
14 weeks
期刊介绍: Cancer Imaging and Diagnosis is dedicated to the publication of results from clinical and research studies applied to cancer diagnosis and treatment. The section aims to publish studies from the entire field of cancer imaging: results from routine use of clinical imaging in both radiology and nuclear medicine, results from clinical trials, experimental molecular imaging in humans and small animals, research on new contrast agents in CT, MRI, ultrasound, publication of new technical applications and processing algorithms to improve the standardization of quantitative imaging and image guided interventions for the diagnosis and treatment of cancer.
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