Role of Mitochondria-Related Genes in NSCLC: Prognostic Implications and Immune Microenvironment Influence

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

International Journal of Clinical Practice Pub Date : 2025-04-07 DOI:10.1155/ijcp/1337914

Zhenye Pu, Bin Liu, Jin Fang, Yang Hu, Tao Xue, Hongyan Li

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Abstract

Background: The role of mitochondria-related genes on non-small-cell lung cancer (NSCLC), which encompasses lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), remains inadequately understood. This study investigates their influence on prognosis, immune microenvironment, and response to immunotherapy.

Methods: We analyzed NSCLC data from The Cancer Genome Atlas to assess gene expression differences, Kaplan–Meier survival curves, and Cox regression. A prognostic model was developed using machine learning techniques. Functional enrichment and pathway analyses were performed using Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Single-cell RNA sequencing data from the TISCH2 database were examined to elucidate key gene expressions. Tumor Mutation Burden and differential mutation frequencies were evaluated. The ESTIMATE and TIDE algorithms were utilized to analyze the immune microenvironment and predict responses to immunotherapy.

Results: Significant mitochondria-related genes were identified in both LUAD and LUSC. The StepCox [both] + Ridge model, which included 13 genes, exhibited the highest prognostic accuracy. Functional analyses indicated that these genes are involved in KRAS signaling, angiogenesis, and glycolysis. Single-cell analysis revealed that KLK6 expression is primarily localized in malignant and epithelial cells. Mutation analysis indicated that PTEN and ASPM mutations were more prevalent in low-risk groups, whereas CACNA1C and CSMD1 mutations were more common in high-risk groups. Nine genes showed strong correlations with immune scores. TIDE analysis suggested that high-risk patients may have a better response to immunotherapy, a finding corroborated by submap analysis in high-risk LUSC patients.

Conclusion: Mitochondria-related genes significantly impact the prognosis of NSCLC and may influence the immune microenvironment and responses to immunotherapy. These findings enhance our understanding of NSCLC and suggest potential targets for future therapeutic interventions.

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线粒体相关基因在非小细胞肺癌中的作用：预后意义和免疫微环境影响

背景：线粒体相关基因在包括肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）在内的非小细胞肺癌（NSCLC）中的作用仍未充分了解。本研究探讨其对预后、免疫微环境和免疫治疗反应的影响。方法：我们分析了来自癌症基因组图谱的NSCLC数据，以评估基因表达差异、Kaplan-Meier生存曲线和Cox回归。使用机器学习技术开发了一个预测模型。使用基因本体、京都基因与基因组百科全书和基因集富集分析进行功能富集和途径分析。我们检查了来自TISCH2数据库的单细胞RNA测序数据，以阐明关键基因的表达。评估肿瘤突变负荷和差异突变频率。利用ESTIMATE和TIDE算法分析免疫微环境并预测免疫治疗反应。结果：在LUAD和LUSC中均发现了显著的线粒体相关基因。包括13个基因的StepCox [both] + Ridge模型显示出最高的预后准确性。功能分析表明，这些基因参与KRAS信号传导、血管生成和糖酵解。单细胞分析显示，KLK6的表达主要局限于恶性细胞和上皮细胞。突变分析表明，PTEN和ASPM突变在低危人群中更为普遍，而CACNA1C和CSMD1突变在高危人群中更为常见。9个基因与免疫评分有很强的相关性。TIDE分析提示高危患者可能对免疫治疗有更好的反应，这一发现在高危LUSC患者的亚图分析中得到了证实。结论：线粒体相关基因显著影响NSCLC的预后，并可能影响免疫微环境和对免疫治疗的反应。这些发现增强了我们对非小细胞肺癌的认识，并提出了未来治疗干预的潜在目标。

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来源期刊

International Journal of Clinical Practice 医学-医学：内科

CiteScore

5.30

自引率

0.00%

发文量

274

审稿时长

3-8 weeks

期刊介绍： IJCP is a general medical journal. IJCP gives special priority to work that has international appeal. IJCP publishes: Editorials. IJCP Editorials are commissioned. [Peer reviewed at the editor''s discretion] Perspectives. Most IJCP Perspectives are commissioned. Example. [Peer reviewed at the editor''s discretion] Study design and interpretation. Example. [Always peer reviewed] Original data from clinical investigations. In particular: Primary research papers from RCTs, observational studies, epidemiological studies; pre-specified sub-analyses; pooled analyses. [Always peer reviewed] Meta-analyses. [Always peer reviewed] Systematic reviews. From October 2009, special priority will be given to systematic reviews. [Always peer reviewed] Non-systematic/narrative reviews. From October 2009, reviews that are not systematic will be considered only if they include a discrete Methods section that must explicitly describe the authors'' approach. Special priority will, however, be given to systematic reviews. [Always peer reviewed] ''How to…'' papers. Example. [Always peer reviewed] Consensus statements. [Always peer reviewed] Short reports. [Always peer reviewed] Letters. [Peer reviewed at the editor''s discretion] International scope IJCP publishes work from investigators globally. Around 30% of IJCP articles list an author from the UK. Around 30% of IJCP articles list an author from the USA or Canada. Around 45% of IJCP articles list an author from a European country that is not the UK. Around 15% of articles published in IJCP list an author from a country in the Asia-Pacific region.