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检测肺腺癌中与脂肪酸代谢相关的基因作为临床预后和免疫治疗靶点的生物标志物。

Detection of the Fatty Acid Metabolism-Linked Genes in Lung Adenocarcinoma as Biomarkers for Clinical Prognosis and Immunotherapeutic Targets.

机构信息

Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China.

Department of Cardiovascular and Thoracic Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing University, Nanjing, Jiangsu Province, China.

出版信息

Clin Respir J. 2024 Oct;18(10):e70013. doi: 10.1111/crj.70013.

Abstract

BACKGROUND

Lung cancer, on a global scale, leads to the most common cases of cancer mortalities. Novel therapeutic approaches are urgently needed to disrupt this lethal disease. The rapid development of tumor immunology combining breakthroughs involving fatty acid metabolism brings possibilities. Directing fatty acid metabolism is supposed to help discover potential prognostic biomarkers and treatment targets for lung cancer.

METHODS

Through searching the GSE140797 dataset, we identified genes related to fatty acid metabolism as well as fatty acid metabolism-related differentially expressed genes (DEGs). We applied various methods to ascertain the independent prognostic value of the DEGs. The methods we utilized entail prognostic analysis, differential expression analysis, as well as univariate and multivariate Cox regression analyses. The lasso Cox regression model was utilized in examining how DEGs correlate with the immune score, immune checkpoint, ferroptosis, methylation, and OCLR score. The expression levels of ACAT1 and ACSL3 in tissues derived from normal lung and lung adenocarcinoma (LUAD) tissues were compared by qRT-PCR.

RESULTS

In this study, ACSL3 and ACAT1 were identified as fatty acid metabolism-related genes utilizing independent prognostic value and as a result, the risk prognostic model was built using these factors. qRT-PCR results implied that ACSL3 and ACAT1 expressions were upregulated and downregulated, correspondingly in tumor tissues. Additional evaluations suggested that ACSL3 and ACAT1 were affirmed to be remarkably correlated with the immune score, methylation, immune checkpoint, OCLR score, and ferroptosis.

CONCLUSIONS

ACSL3 and ACAT1 were effective prognostic biomarkers and potential immunotherapeutic targets in LUAD.

摘要

背景

在全球范围内,肺癌导致的癌症死亡率最高。急需新的治疗方法来打破这种致命疾病。肿瘤免疫学的快速发展与脂肪酸代谢的突破相结合带来了可能性。指导脂肪酸代谢有望帮助发现肺癌的潜在预后生物标志物和治疗靶点。

方法

通过搜索 GSE140797 数据集,我们确定了与脂肪酸代谢相关的基因以及与脂肪酸代谢相关的差异表达基因(DEGs)。我们应用各种方法来确定 DEGs 的独立预后价值。我们使用的方法包括预后分析、差异表达分析以及单变量和多变量 Cox 回归分析。Lasso Cox 回归模型用于检查 DEGs 与免疫评分、免疫检查点、铁死亡、甲基化和 OCLR 评分的相关性。通过 qRT-PCR 比较正常肺组织和肺腺癌(LUAD)组织中 ACAT1 和 ACSL3 的表达水平。

结果

在这项研究中,ACSL3 和 ACAT1 被确定为具有独立预后价值的脂肪酸代谢相关基因,并因此使用这些因素构建了风险预后模型。qRT-PCR 结果表明,ACSL3 和 ACAT1 在肿瘤组织中相应地上调或下调。进一步评估表明,ACSL3 和 ACAT1 与免疫评分、甲基化、免疫检查点、OCLR 评分和铁死亡显著相关。

结论

ACSL3 和 ACAT1 是 LUAD 中有效的预后生物标志物和潜在的免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a11/11424681/13f09763ca1c/CRJ-18-e70013-g003.jpg

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