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线粒体自噬相关基因CHDH预测口腔鳞状细胞癌的预后和免疫反应并在体内外抑制其增殖和迁移

Mitophagy-Related Gene CHDH Predicts Prognosis and Immune Response and Inhibits Proliferation and Migration in vitro and in vivo of Oral Squamous Cell Carcinoma.

作者信息

Chen Lingke, Zhou Zheng, Guo Lian, He Zhongrun, Luo Wen, Fu Ying, Xiao Qiyu, Liu Bo, Huang Pengxin

机构信息

Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, People's Republic of China.

Department of Stomatology, Changsha Central Hospital, Changsha, People's Republic of China.

出版信息

J Inflamm Res. 2025 May 26;18:6831-6851. doi: 10.2147/JIR.S516427. eCollection 2025.

DOI:10.2147/JIR.S516427
PMID:40453965
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12124313/
Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Mitophagy is a special type of cellular autophagy that plays an important role in tumors, but its role in OSCC is still unclear.

METHODS

Mitophagy-related genes (MRGs) were obtained from the GeneCards database. Differential expression analysis was used to identify differentially expressed genes (DEGs) in tumor samples and normal samples. Univariate Cox regression was then performed on the DEGs to determine prognostic MRGs, which were used to compare CNV mutation frequencies and construct consensus cluster analysis. Risk models were constructed to evaluate the prognosis and immune status of OSCC patients. Univariate and multivariate Cox regression analyses were performed to determine MRGs that independently predicted OSCC prognosis. The expression levels of genes and their effects on OSCC proliferation, migration, and invasion were further validated by in vitro and in vivo studies.

RESULTS

We identified 298 DEGs associated with OSCC survival, and 8 genes were used to create a risk model that can accurately predict the prognosis of OSCC patients, which can accurately assess the immune status of patients with different risks. OSCC patients were clustered into 2 subtypes, and there were significant differences between the two subtypes. Drug sensitivity analysis was used to select 72 sensitive drugs for the low-risk group and 9 sensitive drugs for the high-risk group. Choline dehydrogenase (CHDH) was identified as a reliable and independent predictor of OSCC. CHDH overexpression significantly inhibited OSCC cell proliferation, migration, colony formation, and tumor growth.

CONCLUSION

This study's prediction model, created using MRGs, may accurately predict the prognosis and immune response of patients with OSCC. CHDH is essential to the development and progression of OSCC and can be a potential target for treating OSCC.

摘要

背景

口腔鳞状细胞癌(OSCC)是一种常见的头颈部癌症,发病率和死亡率都很高。线粒体自噬是细胞自噬的一种特殊类型,在肿瘤中起重要作用,但其在OSCC中的作用仍不清楚。

方法

从GeneCards数据库中获取线粒体自噬相关基因(MRGs)。采用差异表达分析来鉴定肿瘤样本和正常样本中的差异表达基因(DEGs)。然后对DEGs进行单变量Cox回归分析以确定预后MRGs,用于比较拷贝数变异(CNV)突变频率并构建共识聚类分析。构建风险模型以评估OSCC患者的预后和免疫状态。进行单变量和多变量Cox回归分析以确定独立预测OSCC预后的MRGs。通过体外和体内研究进一步验证基因的表达水平及其对OSCC增殖、迁移和侵袭的影响。

结果

我们鉴定出298个与OSCC生存相关的DEGs,并使用8个基因创建了一个风险模型,该模型可以准确预测OSCC患者的预后,还能准确评估不同风险患者的免疫状态。OSCC患者被聚类为2个亚型,两个亚型之间存在显著差异。药物敏感性分析为低风险组选择了72种敏感药物,为高风险组选择了9种敏感药物。胆碱脱氢酶(CHDH)被确定为OSCC可靠且独立的预测指标。CHDH过表达显著抑制OSCC细胞增殖、迁移、集落形成和肿瘤生长。

结论

本研究使用MRGs创建的预测模型可能准确预测OSCC患者的预后和免疫反应。CHDH对OSCC的发生和发展至关重要,可成为治疗OSCC的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4869/12124313/1fc2a2eb46f7/JIR-18-6831-g0010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4869/12124313/cc6234469b71/JIR-18-6831-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4869/12124313/1fc2a2eb46f7/JIR-18-6831-g0010.jpg

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