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基于线粒体代谢相关基因的喉鳞状细胞癌预后模型

A prognostic model for laryngeal squamous cell carcinoma based on the mitochondrial metabolism-related genes.

作者信息

Hu Wei-Ming, Jiang Wen-Jing

机构信息

Head and Neck & Otolaryngology Center, Plastic Surgery Center, Cancer Center, Department of Otolaryngology, Zhejiang Provincial People's Hospital, Hangzhou, China.

出版信息

Transl Cancer Res. 2025 Feb 28;14(2):966-979. doi: 10.21037/tcr-24-1436. Epub 2025 Feb 18.

Abstract

BACKGROUND

Mitochondrial metabolism-related genes (MMRGs) have emerged as potential therapeutic targets in cancer. This study aimed to construct a prognosis model based on MMRGs for patients with laryngeal squamous cell carcinoma (LSCC).

METHODS

Differentially expressed MMRGs in LSCC were identified from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB). Their functions were characterized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A prognostic model was established using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses, and its performance was evaluated using Kaplan-Meier and receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA) was performed to elucidate the biological pathways associated with the hub prognostic MMRGs. Genetic perturbation similarity analysis (GPSA) was used to determine the regulatory network of hub genes. Additionally, the correlation of the hub MMRGs with the immune microenvironment and drug sensitivity was investigated.

RESULTS

We identified 308 differentially expressed MMRGs, enriched in various metabolic processes and pathways. The prognostic model comprising four hub MMRGs (, , , and ) accurately predicted patient outcomes, with the high-risk group exhibiting poorer survival. Additionally, high expression of and while low expression of and indicated better prognosis for LSCC patients. GSEA revealed pathways correlated with each prognostic MMRG, such as PI3K-AKT-mTOR signaling pathways, while GPSA identified key regulatory genes interacting with four hub MMRGs. Furthermore, differences in the tumor immune microenvironment and somatic mutation profiles were observed between high- and low-risk groups. Finally, the correlation of four hub MMRGs with 30 drug sensitivity was revealed.

CONCLUSIONS

This study highlights the prognostic significance of MMRGs in LSCC and underscores their potential as biomarkers for LSCC therapy.

摘要

背景

线粒体代谢相关基因(MMRGs)已成为癌症潜在的治疗靶点。本研究旨在构建基于MMRGs的喉鳞状细胞癌(LSCC)患者预后模型。

方法

从癌症基因组图谱(TCGA)和分子特征数据库(MSigDB)中鉴定LSCC中差异表达的MMRGs。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)对其功能进行表征。使用单变量、最小绝对收缩和选择算子(LASSO)以及多变量Cox回归分析建立预后模型,并使用Kaplan-Meier曲线和受试者工作特征(ROC)曲线评估其性能。进行基因集富集分析(GSEA)以阐明与核心预后MMRGs相关的生物学途径。使用基因扰动相似性分析(GPSA)确定核心基因的调控网络。此外,研究了核心MMRGs与免疫微环境和药物敏感性的相关性。

结果

我们鉴定出308个差异表达的MMRGs,它们富集于各种代谢过程和途径中。由四个核心MMRGs( 、 、 和 )组成的预后模型准确预测了患者的预后,高危组的生存率较差。此外, 和 的高表达以及 和 的低表达表明LSCC患者的预后较好。GSEA揭示了与每个预后MMRGs相关的途径,如PI3K-AKT-mTOR信号通路,而GPSA确定了与四个核心MMRGs相互作用的关键调控基因。此外,在高危组和低危组之间观察到肿瘤免疫微环境和体细胞突变谱存在差异。最后,揭示了四个核心MMRGs与30种药物敏感性的相关性。

结论

本研究突出了MMRGs在LSCC中的预后意义,并强调了它们作为LSCC治疗生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d0/11912054/3a73a509f306/tcr-14-02-966-f1.jpg

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