线粒体脂质代谢基因作为肝细胞癌的诊断和预后指标

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-03-01 DOI:10.2174/1389202924666230914110649

Xuejing Li, Ying Tan, Bihan Liu, Houtian Guo, Yongjian Zhou, Jianhui Yuan, Feng Wang

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引用次数: 0

摘要

背景:由于肝细胞癌(HCC)的异质性，迫切需要可靠的诊断和预后。线粒体介导的脂质代谢异常影响HCC的发生和发展。目的:本研究旨在探讨线粒体脂质代谢(MTLM)基因作为HCC诊断和独立预后生物标志物的潜力。方法:从基因表达综合(GEO)和基因集富集分析(GSEA)数据库中筛选MTLM基因，并在肿瘤基因组图谱计划(TCGA)和广西医科大学附属肿瘤医院(GXMU)队列中评估其诊断价值。利用TCGA数据集构建基因标记，并研究预后意义、免疫浸润和拷贝数改变。通过GEO、国际癌症基因组联盟(ICGC)和GXMU队列证实了预后特征的有效性。结果:诊断性受试者工作特征(ROC)曲线显示8个MTLM基因对HCC具有良好的诊断价值。基于TCGA数据，采用lasso回归算法构建了具有鲁棒预测值的5个MTLM基因的预后特征。逐步回归模型结果显示，与单一风险评分相比，特征与常规临床参数的组合具有更高的曲线下面积(AUC)。进一步构建了预测HCC生存概率的nomogram，校正曲线具有较好的预测能力。最后，风险评分还揭示了两个不同风险组之间不同的免疫和突变状态。结论:mtlt相关基因可作为HCC诊断和预后的生物标志物和新的治疗靶点，有助于进一步了解HCC的分子发病机制和提供潜在的治疗策略。

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Mitochondrial Lipid Metabolism Genes as Diagnostic and Prognostic Indicators in Hepatocellular Carcinoma

Background: Due to the heterogeneity of Hepatocellular carcinoma (HCC), there is an urgent need for reliable diagnosis and prognosis. Mitochondria-mediated abnormal lipid metabolism affects the occurrence and progression of HCC. Objective: This study aims to investigate the potential of mitochondrial lipid metabolism (MTLM) genes as diagnostic and independent prognostic biomarkers for HCC. Methods: MTLM genes were screened from the Gene Expression Omnibus (GEO) and Gene Set Enrichment Analysis (GSEA) databases, followed by an evaluation of their diagnostic values in both The Cancer Genome Atlas Program (TCGA) and the Affiliated Cancer Hospital of Guangxi Medical University (GXMU) cohort. The TCGA dataset was utilized to construct a gene signature and investigate the prognostic significance, immune infiltration, and copy number alterations. The validity of the prognostic signature was confirmed through GEO, International Cancer Genome Consortium (ICGC), and GXMU cohorts. Results: The diagnostic receiver operating characteristic (ROC) curve revealed that eight MTLM genes have excellent diagnostic of HCC. A prognostic signature comprising 5 MTLM genes with robust predictive value was constructed using the lasso regression algorithm based on TCGA data. The results of the Stepwise regression model showed that the combination of signature and routine clinical parameters had a higher area under the curve (AUC) compared to a single risk score. Further, a nomogram was constructed to predict the survival probability of HCC, and the calibration curves demonstrated a perfect predictive ability. Finally, the risk score also unveiled the different immune and mutation statuses between the two different risk groups. Conclusion: MTLT-related genes may serve as diagnostic and prognostic biomarkers for HCC as well as novel therapeutic targets, which may be beneficial for facilitating further understanding the molecular pathogenesis and providing potential therapeutic strategies for HCC.

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.