基于生物信息学的肝细胞癌组织miR-1180 表达与临床意义 分析
| 作者: |
1,2余斌,
1,2丁佑铭,
3廖晓锋
1 武汉大学人民医院 肝胆腔镜外科，湖北 武汉 430060 2 消化系统疾病湖北省重点实验室，湖北 武汉 430060 3 湖北省襄阳市中心医院 普通外科，湖北 襄阳 441021 |
| 通讯: |
丁佑铭
Email: dingym@whu.edu.cn |
| DOI: | 10.3978/.2018.07.010 |
摘要
目的：通过生物信息学数据分析探讨肝细胞癌（HCC）组织中 miR-1180 的表达及其临床意义。
方法：下载 GEO（Gene Expression Omnibus）和 TCGA（The Cancer Genome Atlas）相关数据集，比较 HCC 组织和癌旁组织中 miR-1180 表达量，并分析 miR-1180 表达量与肝癌患者临床病理特征及预后之间的相关性。利用生物信息学方法对 miR-1180 的靶基因进行预测及功能富集分析，并结合预后分析结果筛选 miR-1180 关键靶基因。
结果：miR-1180 在 HCC 组织中较癌旁组织高表达，且对于 HCC 具有良好的诊断效能（AUC>0.8，均P<0.05）；miR-1180 的表达量与患者年龄、肿瘤家族史、肿瘤分化程度以及 AFP 等指标明显有关（均P<0.05）。生存分析表明 HCC 组织中 miR-1180 高表达是影响 HCC 患者预后的独立危险因素（P<0.05）。富集分析提示 miR-1180 的靶基因主要富集于脂质代谢、细胞迁移、转录调控等功能和脂肪酸降解等通路。PPARGC1A、ALDH2、SARDH、HMGCS2、ESR1、ETS2 等为 miR-1180 关键靶基因，在 HCC 组织中均表达下调（均 P<0.05），且相对低表达者预后较差（均 P<0.05）。
结论：miR-1180 在 HCC 组织中表达升高，其可能作为一种促癌 miRNA 参与 HCC 的发生、发展，并具有成为 HCC 诊断标志物、预后指标及治疗靶点的潜在应用价值。
关键词：
癌，肝细胞；微 RNAs；预后；计算生物学
方法：下载 GEO（Gene Expression Omnibus）和 TCGA（The Cancer Genome Atlas）相关数据集，比较 HCC 组织和癌旁组织中 miR-1180 表达量，并分析 miR-1180 表达量与肝癌患者临床病理特征及预后之间的相关性。利用生物信息学方法对 miR-1180 的靶基因进行预测及功能富集分析，并结合预后分析结果筛选 miR-1180 关键靶基因。
结果：miR-1180 在 HCC 组织中较癌旁组织高表达，且对于 HCC 具有良好的诊断效能（AUC>0.8，均P<0.05）；miR-1180 的表达量与患者年龄、肿瘤家族史、肿瘤分化程度以及 AFP 等指标明显有关（均P<0.05）。生存分析表明 HCC 组织中 miR-1180 高表达是影响 HCC 患者预后的独立危险因素（P<0.05）。富集分析提示 miR-1180 的靶基因主要富集于脂质代谢、细胞迁移、转录调控等功能和脂肪酸降解等通路。PPARGC1A、ALDH2、SARDH、HMGCS2、ESR1、ETS2 等为 miR-1180 关键靶基因，在 HCC 组织中均表达下调（均 P<0.05），且相对低表达者预后较差（均 P<0.05）。
结论：miR-1180 在 HCC 组织中表达升高，其可能作为一种促癌 miRNA 参与 HCC 的发生、发展，并具有成为 HCC 诊断标志物、预后指标及治疗靶点的潜在应用价值。
Analysis of miR-1180 expression in hepatocellular carcinoma tissue and its clinical significance based on bioinformatics
CorrespondingAuthor:Youming DING Email: dingym@whu.edu.cn
Abstract
Objective: To analyze the expression of miR-1180 in hepatocellular carcinoma (HCC) tissue and its clinical signifi cance through bioinformatics data analysis.
Methods: Th e relevant data sets from GEO (Gene Expression Omnibus) and TCGA (Cancer Genome Atlas) database were downloaded, and then the expression levels of miR-1180 in HCC tissues and cancer adjacent liver tissues were compared, and the relations of miR-1180 expression level with clinicopathologic characteristics and prognosis of the patients were also analyzed. The prediction of potential target genes of miR-1180 and functional enrichment analyses of the target genes were performed by bioinformatics analysis. Furthermore, the key target genes of miR-1180 were screened based on survival analysis.
Results: The expression levels of miR-1180 were significantly up-regulated in HCC tissues compared with the cancer adjacent tissues, which had good diagnostic efficiencies for HCC (AUC>0.8, all P<0.05). The miR-1180 expression level was significantly associated with age, family history of cancer, degree of tumor differentiation and AFP of the patients (all P<0.05). Survival analysis showed that miR-1180 overexpression was independent risk factor for diagnosis in HCC patients (P<0.05). Enrichment analyses revealed that the target genes of miR-1180 were mainly enriched in the pathways associated with lipid metabolism, cell migration, transcriptional regulation and fatty acid degradation. PPARGC1A, ALDH2, SARDH, HMGCS2, ESR1 and ETS2 were the key target genes of miR-1180, with significantly decreased down-regulation in HCC tissue (all P<0.05), and patients with low expressions of these genes had relatively poor prognosis (all P<0.05).
Conclusion: The miR-1180 expression is increased in HCC tissue. It may participate in the occurrence and development of HCC as an oncogenic miRNA, and also has potential value as a diagnostic biomarker, prognostic indicator and therapeutic target for HCC.
Keywords：
Carcinoma
Hepatocellular; MicroRNAs; Prognosis; Computational Biology
Methods: Th e relevant data sets from GEO (Gene Expression Omnibus) and TCGA (Cancer Genome Atlas) database were downloaded, and then the expression levels of miR-1180 in HCC tissues and cancer adjacent liver tissues were compared, and the relations of miR-1180 expression level with clinicopathologic characteristics and prognosis of the patients were also analyzed. The prediction of potential target genes of miR-1180 and functional enrichment analyses of the target genes were performed by bioinformatics analysis. Furthermore, the key target genes of miR-1180 were screened based on survival analysis.
Results: The expression levels of miR-1180 were significantly up-regulated in HCC tissues compared with the cancer adjacent tissues, which had good diagnostic efficiencies for HCC (AUC>0.8, all P<0.05). The miR-1180 expression level was significantly associated with age, family history of cancer, degree of tumor differentiation and AFP of the patients (all P<0.05). Survival analysis showed that miR-1180 overexpression was independent risk factor for diagnosis in HCC patients (P<0.05). Enrichment analyses revealed that the target genes of miR-1180 were mainly enriched in the pathways associated with lipid metabolism, cell migration, transcriptional regulation and fatty acid degradation. PPARGC1A, ALDH2, SARDH, HMGCS2, ESR1 and ETS2 were the key target genes of miR-1180, with significantly decreased down-regulation in HCC tissue (all P<0.05), and patients with low expressions of these genes had relatively poor prognosis (all P<0.05).
Conclusion: The miR-1180 expression is increased in HCC tissue. It may participate in the occurrence and development of HCC as an oncogenic miRNA, and also has potential value as a diagnostic biomarker, prognostic indicator and therapeutic target for HCC.