基于生物信息学和分子对接筛选结直肠腺癌的潜在生物标志物及其靶向药物

Comprehensive analysis of biomarkers and targeted drug of COAD based on bioinformatics and molecular docking

[目的]获取结直肠癌(Colon adenocarcinoma,COAD)的潜在生物标志物及其靶向药物。[方法]用R和Cytoscape 3.8.2软件分析临床数据库中56例COAD患者和45例正常样本的转录组数据,获取生物标志物及其共表达基因并分析其生物功能。通过miRWalk和miRTarBase数据库得到与COAD生存预后相关的miRNAs并分析它们的功能。利用分子对接筛选与所获生物标志物具有较好结合能力的靶向中药小分子化合物。[结果]共筛选得到179个差异表达基因,包括49个高表达基因和130个低表达基因。STRING和Cytoscape 3.8.2所得30个Hubba基因中仅CLCA1符合Cox模型(C-index:0.708(0.632-1),P<0.001)。CLCA1及其共表达基因主要参与氯离子跨膜转运过程,与肿瘤的发生发展密切相关(P<0.01)。mRNA-miRNA网络中与CLCA1密切相关的10个miRNA主要参与肿瘤细胞的增殖,凋亡和血管的形成。且甘草次酸、小檗碱和雷公藤红素被证实与CLCA1结合较牢。[结论]CLCA1是COAD的潜在生物标志物,且甘草次酸、小檗碱和雷公藤红素是CLCA1的潜在靶向药物。

[Objective] To mine the new biomarkers and targeted drugs of colon adenocarcinoma.[Method] R and Cytoscape 3.8.1 software were used to analyze the transcriptome data of 56 COAD patients and 45 normal samples in the clinical database,to obtain biomarkers and their co-expressed genes,and to analyze their biological functions.The miRNAs associated with survival and prognosis in COAD were obtained through miRWalk and miRTarBase databases and their functions were analyzed.Molecular docking was used to screen targeted small molecule compounds of traditional Chinese medicine with good binding ability to the obtained biomarkers.[Result] A total of 179 differentially expressed genes were screened,including 49 up-expressed genes and 130 down-expressed genes.Among the 30 Hubba genes obtained by STRING and Cytoscape 3.8.1,only CLCA1 fit the Cox model(C-index:0.708(0.632-1),P<0.001).CLCA1 and its co-expressed genes were mainly involved in the chloride ion transmembrane transport process,and were closely related to the occurrence and development of tumors(P<0.01).10 miRNAs closely related to CLCA1 in the mRNA-miRNA network were mainly involved in tumor cell proliferation,apoptosis and angiogenesis.Glycyrrhetinic acid,berberine and triptolide had good affinity with CLCA1 and are potential targeted drugs.[Conclusion]CLCA1 is a potential biomarker for COAD,and glycyrrhetinic acid,berberine and triptolide are potential targeted drugs for CLCA1.