Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Int J Med Sci. 2021 Sep 7;18(16):3631-3643. doi: 10.7150/ijms.63953. eCollection 2021.
Acyl-CoA dehydrogenase short-chain (ACADS) is a crucial enzyme in the fatty acid metabolism pathway located in mitochondria. However, the expression level and prognostic value of ACADS in colorectal cancer (CRC) remain unclear. The mRNA and protein expression data of ACADS was obtained from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Oncomine. Prognostic values of ACADS were calculated using Kaplan-Meier survival analysis. Correlations between ACADS and immune infiltration were estimated using TIMER, CIBERSORT, EPIC, quanTIseq, and xCell. The UALCAN and MEXPRESS databases were utilized for Methylation analysis. The co-expression analysis based on mRNA expression and interaction network of ACADS were performed via several online tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on ACADS co-expressed genes were performed using the Metascape. The expression analysis demonstrated that ACADS was down-regulated in CRC tissues compared with paired normal tissue. Expression of ACADS was found to be significantly associated with clinical cancer stages and the consensus molecular subgroups (CMS) constituent ratio in CRC patients. Besides, lower ACADS expression was found to predict poor prognosis and be significantly associated with common immune checkpoint genes and MMR genes in CRC. ACADS expression levels were positively related to B cells, CD4 T cells, CD8 T cells, M1 macrophages, neutrophils, and Tregs, while negatively correlated with M0 macrophages, M2 macrophages. The methylation level of ACADS in normal tissues was significantly higher than that in tumor tissues, and several methylation sites were identified. The enrichment analysis suggested the co-expressed genes mainly enriched in cell mitochondrial metabolism. The present study provided multilevel evidences for expression of ACADS in CRC and the function of ACADS in prognostic prediction, immune infiltration, and methylation. ACADS might have the potential as the novel biomarker and therapeutic target in CRC patients.
酰基辅酶 A 脱氢酶短链 (ACADS) 是位于线粒体中的脂肪酸代谢途径中的关键酶。然而，ACADS 在结直肠癌 (CRC) 中的表达水平和预后价值尚不清楚。ACADS 的 mRNA 和蛋白质表达数据来自癌症基因组图谱 (TCGA)、临床蛋白质肿瘤分析联盟 (CPTAC) 和 Oncomine。使用 Kaplan-Meier 生存分析计算 ACADS 的预后值。使用 TIMER、CIBERSORT、EPIC、quanTIseq 和 xCell 估计 ACADS 与免疫浸润的相关性。使用 UALCAN 和 MEXPRESS 数据库进行甲基化分析。基于 mRNA 表达的共表达分析和 ACADS 的互作网络通过几个在线工具进行。使用 Metascape 对 ACADS 共表达基因进行基因本体论 (GO) 和京都基因与基因组百科全书 (KEGG) 分析。表达分析表明，ACADS 在 CRC 组织中较配对正常组织下调。ACADS 的表达与 CRC 患者的临床癌症分期和共识分子亚群 (CMS) 组成比例显著相关。此外，较低的 ACADS 表达预示着不良预后，与 CRC 中的常见免疫检查点基因和 MMR 基因显著相关。ACADS 表达水平与 B 细胞、CD4 T 细胞、CD8 T 细胞、M1 巨噬细胞、中性粒细胞和 Tregs 呈正相关，与 M0 巨噬细胞、M2 巨噬细胞呈负相关。正常组织中 ACADS 的甲基化水平明显高于肿瘤组织，并且鉴定出几个甲基化位点。富集分析表明，共表达基因主要富集在细胞线粒体代谢中。本研究为 ACADS 在 CRC 中的表达及其在预后预测、免疫浸润和甲基化中的功能提供了多层次的证据。ACADS 可能有作为 CRC 患者新的生物标志物和治疗靶点的潜力。
