Table_1_Fatty Acid Metabolism-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Patients With Colorectal Cancer.xlsx

Abnormal metabolism, including abnormal fatty acid metabolism, is an emerging hallmark of cancer. The current study sought to investigate the potential prognostic value of fatty acid metabolism-related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). To this end, we obtained the gene expression data and clinical data of patients with CRC from The Cancer Genome Atlas (TCGA) database. Through gene set variation analysis (GSVA), we found that the fatty acid metabolism pathway was related to the clinical stage and prognosis of patients with CRC. After screening differentially expressed RNAs, we constructed a fatty acid metabolism-related competing endogenous RNA (ceRNA) network based on the miRTarBase, miRDB, TargetScan, and StarBase databases. Next, eight fatty acid metabolism-related lncRNAs included in the ceRNA network were identified to build a prognostic signature with Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, and a nomogram was established based on the lncRNA signature and clinical variables. The signature and nomogram were further validated by Kaplan–Meier survival analysis, Cox regression analysis, calibration plots, receiver operating characteristic (ROC) curves, decision curve analysis (DCA). Besides, the TCGA internal and the quantitative real-time polymerase chain reaction (qRT-PCR) external cohorts were applied to successfully validate the robustness of the signature and nomogram. Finally, in vitro assays showed that knockdown of prognostic lncRNA TSPEAR-AS2 decreased the triglyceride (TG) content and the expressions of fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) in CRC cells, which indicated the important role of lncRNA TSPEAR-AS2 in modulating fatty acid metabolism of CRC. The result of Oil Red O staining showed that the lipid content in lncRNA TSPEAR-AS2 high expression group was higher than that in lncRNA TSPEAR-AS2 low expression group. Our study may provide helpful information for fatty acid metabolism targeting therapies in CRC.异常代谢（包括异常脂肪酸代谢）是新近发现的癌症标志性特征。本研究旨在探讨脂肪酸代谢相关长链非编码RNA（long noncoding RNAs，lncRNAs）在结直肠癌（colorectal cancer，CRC）中的潜在预后价值。为此，我们从癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库中获取了结直肠癌患者的基因表达数据与临床资料。通过基因集变异分析（gene set variation analysis，GSVA），我们发现脂肪酸代谢通路与结直肠癌患者的临床分期及预后相关。筛选差异表达RNA后，我们基于miRTarBase、miRDB、TargetScan及StarBase数据库构建了脂肪酸代谢相关竞争性内源RNA（competing endogenous RNA，ceRNA）调控网络。随后，我们从该ceRNA网络中筛选出8个脂肪酸代谢相关长链非编码RNA，通过Cox回归及最小绝对收缩和选择算子（least absolute shrinkage and selection operator，LASSO）回归分析构建了预后特征模型，并基于该长链非编码RNA特征与临床变量建立了列线图（nomogram）。我们通过卡普兰-迈耶（Kaplan-Meier）生存分析、Cox回归分析、校准曲线、受试者工作特征（ROC）曲线及决策曲线分析（decision curve analysis，DCA）对该预后特征模型与列线图进行了进一步验证。此外，我们通过TCGA内部队列及定量实时聚合酶链反应（quantitative real-time polymerase chain reaction，qRT-PCR）外部队列成功验证了该预后特征模型与列线图的稳健性。最后，体外实验结果显示，敲低预后相关长链非编码RNA TSPEAR-AS2可降低结直肠癌细胞内的甘油三酯（triglyceride，TG）含量，以及脂肪酸合酶（fatty acid synthase，FASN）与乙酰辅酶A羧化酶1（acetyl-CoA carboxylase 1，ACC1）的表达水平，这表明TSPEAR-AS2在调控结直肠癌脂肪酸代谢中发挥重要作用。油红O染色结果显示，TSPEAR-AS2高表达组的脂质含量高于TSPEAR-AS2低表达组。本研究可为结直肠癌靶向脂肪酸代谢的治疗策略提供有益参考。