Parsazad Ehsan, Esrafili Farina, Yazdani Behnaz, Ghafarzadeh Saghi, Razmavar Namdar, Sirous Hajar
Department of Bioscience and Biotechnology, Malek Ashtar University, Tehran, I.R. Iran.
Medvac Biopharma Company, Alborz Province, I.R. Iran.
Res Pharm Sci. 2023 Jun 1;18(4):413-429. doi: 10.4103/1735-5362.378088. eCollection 2023 Jul-Aug.
Acyl-CoA synthetase (ACS) enzymes play an important role in the activation of fatty acids. While many studies have found correlations between the expression levels of ACS enzymes with the progression, growth, and survival of cancer cells, their role and expression patterns in colon adenocarcinoma are still greatly unknown and demand further investigation.
The expression data of colon adenocarcinoma samples were downloaded from the Cancer Genome Atlas (TCGA) database. Normalization and differential expression analysis were performed to identify differentially expressed genes (DEGs). Gene set enrichment analysis was applied to identify top enriched genes from ACS enzymes in cancer samples. Gene ontology and protein-protein interaction analyses were performed for the prediction of molecular functions and interactions. Survival analysis and receiver operating characteristic test (ROC) were performed to find potential prognostic and diagnostic biomarkers.
FINDINGS/RESULTS: ACSL6 and ACSM5 genes demonstrated more significant differential expression and LogFC value compared to other ACS enzymes and also achieved the highest enrichment scores. Gene ontology analysis predicted the involvement of top DEGs in fatty acids metabolism, while protein-protein interaction network analysis presented strong interactions between ACSLs, ACSSs, ACSMs, and ACSBG enzymes with each other. Survival analysis suggested ACSM3 and ACSM5 as potential prognostic biomarkers, while the ROC test predicted stronger diagnostic potential for ACSM5, ACSS2, and ACSF2 genes.
Our findings revealed the expression patterns, prognostic, and diagnostic biomarker potential of ACS enzymes in colon adenocarcinoma. ACSM3, ACSM5, ACSS2, and ACSF2 genes are suggested as possible prognostic and diagnostic biomarkers.
酰基辅酶A合成酶(ACS)在脂肪酸活化过程中发挥重要作用。尽管许多研究发现ACS酶的表达水平与癌细胞的进展、生长及存活之间存在关联,但其在结肠腺癌中的作用和表达模式仍不清楚,需要进一步研究。
从癌症基因组图谱(TCGA)数据库下载结肠腺癌样本的表达数据。进行归一化和差异表达分析以鉴定差异表达基因(DEG)。应用基因集富集分析从癌症样本中的ACS酶中鉴定高度富集的基因。进行基因本体论和蛋白质-蛋白质相互作用分析以预测分子功能和相互作用。进行生存分析和受试者工作特征测试(ROC)以寻找潜在的预后和诊断生物标志物。
与其他ACS酶相比,ACSL6和ACSM5基因表现出更显著的差异表达和LogFC值,并且富集分数最高。基因本体论分析预测顶级DEG参与脂肪酸代谢,而蛋白质-蛋白质相互作用网络分析显示ACSLs、ACSSs、ACSMs和ACSBG酶之间存在强烈的相互作用。生存分析表明ACSM3和ACSM5是潜在的预后生物标志物,而ROC测试预测ACSM5、ACSS2和ACSF2基因具有更强的诊断潜力。
我们的研究结果揭示了ACS酶在结肠腺癌中的表达模式、预后和诊断生物标志物潜力。建议将ACSM3、ACSM5、ACSS2和ACSF2基因作为可能的预后和诊断生物标志物。