Wang Suyu, Chen Aona, Zhu Wanli, Feng Di, Wei Juan, Li Quanfu, Shi Xuan, Lv Xin, Liu Meiyun
Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.
Front Genet. 2022 Jul 14;13:905508. doi: 10.3389/fgene.2022.905508. eCollection 2022.
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. 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. 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. 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.
肺腺癌(LUAD)是非小细胞肺癌最常见的亚型。脂肪酸代谢参与恶性肿瘤进展。然而,脂肪酸代谢在LUAD中所起的作用仍不清楚。提取了来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的LUAD患者的转录组和临床数据。进行单样本基因集富集分析(ssGSEA)、加权基因共表达网络分析(WGCNA)、单变量Cox回归和套索Cox回归分析,以鉴定影响总生存期(OS)的脂肪酸代谢相关基因,并构建脂肪酸相关风险评分(FARS)模型。基于FARS和其他临床病理特征建立了列线图,并使用受试者工作特征曲线(ROC)和校准图来验证预测准确性。比较了高FARS和低FARS患者的肿瘤微环境(TME)。共鉴定出38个与生存结果独立相关的基因,并将其纳入FARS模型。高FARS患者的OS明显更差。列线图包括FARS和病理分期,预测1年、2年、3年、4年和5年OS的列线图的曲线下面积(AUC)分别为0.789、0.807、0.798、0.809和0.753。校准图也显示出良好的准确性。此外,高FARS样本中程序性死亡受体1配体(PDL1)的表达较高。我们构建了一个可以准确预测LUAD患者生存结果的FARS模型。FARS的基因与肿瘤微环境相关,高FARS患者可能从抗程序性死亡蛋白1(PD1)/程序性死亡受体1配体(PDL1)免疫治疗中获益更多。此外,FARS中影响预后的基因机制值得进一步研究以开发新的基因靶向药物。