Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma

Suyu Wang; Aona Chen; Wanli Zhu; Di Feng; Juan Wei; Quanfu Li; Xuan Shi; Xin Lv; Meiyun Liu

doi:10.3389/fgene.2022.905508

Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma

Front Genet. 2022 Jul 14:13:905508. doi: 10.3389/fgene.2022.905508. eCollection 2022.

Authors

Suyu Wang^{1

2}, Aona Chen³, Wanli Zhu⁴, Di Feng¹, Juan Wei¹, Quanfu Li¹, Xuan Shi¹, Xin Lv¹, Meiyun Liu¹

Affiliations

¹ Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
² Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.
³ Department of General Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.
⁴ Department of General Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Fatty acid metabolism takes part in malignancy progression. However, the roles fatty acid metabolism plays in LUAD are still unclear. Methods: The transcriptomic and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were extracted. ssGSEA, WGCNA, univariable Cox regression, and LASSO Cox regression analyses were performed to identify the fatty acid metabolism-related genes which influenced the overall survival (OS) and build a fatty acid-related risk score (FARS) model. A nomogram was established based on the FARS and other clinicopathological features, and ROC and calibration plots were used to validate the prediction accuracy. The tumor microenvironment (TME) of patients with high and low FARS was compared. Results: A total of 38 genes were identified to be independently related to the survival outcome and put into a FARS model. High FARS patients exhibited significantly worse OS. The nomogram included the FARS and pathological stage, and the AUC of the nomogram predicting 1-, 2-, 3-, 4-, and 5-year OS was 0.789, 0.807, 0.798, 0.809, and 0.753, respectively. Calibration plots also indicated good accuracy. Moreover, the samples of the high FARS had higher expression of PDL1. Conclusion: We constructed a FARS model which could accurately predict the survival outcome of the LUAD patients. The genes of the FARS are related to the tumor microenvironment and patients with high FARS can potentially benefit more from anti-PD1/PDL1 immunotherapy. In addition, the mechanisms of the genes in the FARS affecting prognosis are worthy of further research to develop new gene-targeted drugs.

Keywords: fatty acid metabolism; fatty acid-related risk score; immunotherapy; lung adenocarcinoma; prognosis.