生物信息学筛选姜黄素在肝细胞癌化疗和预后中的新型有前途的靶点。
Bioinformatics screening the novel and promising targets of curcumin in hepatocellular carcinoma chemotherapy and prognosis.
机构信息
Scientific Research Center, The First Affiliated Hospital of Guangdong Pharmaceutical University, Gonghexiheng Street 1, Guangzhou, Guangdong, 510080, P.R. China.
Department of Head and Neck Radiotherapy, Meizhou City People's Hospital, No.6 Building, Huangtang Road 63, Meijiang District, Meizhou, Guangdong, 514031, P.R. China.
出版信息
BMC Complement Med Ther. 2022 Jan 25;22(1):21. doi: 10.1186/s12906-021-03487-9.
BACKGROUND
The aim of present study was to screen the novel and promising targets of curcumin in hepatocellular carcinoma diagnosis and chemotherapy.
METHODS
Potential targets of curcumin were screened from SwissTargetPrediction, ParmMapper and drugbank databases. Potential aberrant genes of hepatocellular carcinoma were screened from Genecards databases. Fifty paired hepatocellular carcinoma patients' gene expression profiles from the GEO database were used to test potential targets of curcumin. Besides, GO analysis, KEGG pathway enrichment analysis and PPI network construction were used to explore the underlying mechanism of candidate hub genes. ROC analysis and Kaplan-Meier analysis were used to evaluate the diagnostic and prognostic value of candidate hub genes, respectively. Real-time PCR was used to verify the results of bioinformatics analysis.
RESULTS
Bioinformatics analysis results suggested that AURKA, CDK1, CCNB1, TOP2A, CYP2B6, CYP2C9, and CYP3A4 genes served as candidate hub genes. AURKA, CDK1, CCNB1 and TOP2A were significantly upregulated and correlated with poor prognosis in hepatocellular carcinoma, AUC values of which were 95.7, 96.9, 98.1 and 96.1% respectively. There was not significant correlation between the expression of CYP2B6 and prognosis of hepatocellular carcinoma, while CYP2C9 and CYP3A4 genes were significantly downregulated and correlated with poor prognosis in hepatocellular carcinoma. AUC values of CYP2B6, CYP2C9, and CYP3A4 were 96.0, 97.0 and 88.0% respectively. In vitro, we further confirmed that curcumin significantly downregulated the expression of AURKA, CDK1, and TOP2A genes, while significantly upregulated the expression of CYP2B6, CYP2C9, and CYP3A4 genes.
CONCLUSIONS
Our results provided a novel panel of AURKA, CDK1, TOP2A, CYP2C9, and CYP3A4 candidate genes for curcumin related chemotherapy of hepatocellular carcinoma.
背景
本研究旨在筛选姜黄素在肝细胞癌诊断和化疗中的新型有前景的靶点。
方法
从 SwissTargetPrediction、ParmMapper 和 drugbank 数据库筛选姜黄素的潜在靶点。从 Genecards 数据库筛选潜在的肝细胞癌异常基因。从 GEO 数据库中使用 50 对肝细胞癌患者的基因表达谱来检测姜黄素的潜在靶点。此外，进行 GO 分析、KEGG 通路富集分析和 PPI 网络构建，以探讨候选关键基因的潜在机制。ROC 分析和 Kaplan-Meier 分析分别用于评估候选关键基因的诊断和预后价值。实时 PCR 用于验证生物信息学分析的结果。
结果
生物信息学分析结果表明，AURKA、CDK1、CCNB1、TOP2A、CYP2B6、CYP2C9 和 CYP3A4 基因作为候选关键基因。AURKA、CDK1、CCNB1 和 TOP2A 在肝细胞癌中显著上调，与预后不良相关，AUC 值分别为 95.7、96.9、98.1 和 96.1%。CYP2B6 的表达与肝细胞癌的预后无显著相关性，而 CYP2C9 和 CYP3A4 基因在肝细胞癌中显著下调，与预后不良相关。CYP2B6、CYP2C9 和 CYP3A4 的 AUC 值分别为 96.0、97.0 和 88.0%。在体外，我们进一步证实姜黄素显著下调 AURKA、CDK1 和 TOP2A 基因的表达，同时显著上调 CYP2B6、CYP2C9 和 CYP3A4 基因的表达。
结论
我们的研究结果为姜黄素相关的肝细胞癌化疗提供了一组新型的 AURKA、CDK1、TOP2A、CYP2C9 和 CYP3A4 候选基因。
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