miR-99a在原发性肝癌组织中的表达及临床意义
| 作者: |
1石小康,
1丁佑铭,
1汪斌,
1余斌,
1徐雨,
1熊豪
1 武汉大学人民医院肝胆外科，武汉 430060 |
| 通讯: |
丁佑铭
Email: dingym@whu.edu.cn |
| DOI: | 10.3978/j.issn.2095-6959.2019.11.005 |
摘要
目的：分析miR-99a在肝癌组织中的表达及临床意义，并通过miR-99a靶基因预测及功能分析探究其在原发性肝癌研究中的潜在价值。方法：从癌症基因组图谱(the Cancer Genome Atlas，TCGA)数据库和基因表达综合(Gene Expression Omnibus，GEO)数据库下载人正常肝组织和肝癌组织中的miR-99a基因表达谱及相应的临床病理资料，分析miR-99a在肝癌及正常肝组织的表达及其与肝癌患者临床病理特征和预后的相关性；同时利用生物信息学方法预测miR-99a的靶基因并对其进行功能富集分析。结果：miR-99a在肝癌组织中表达显著下调(均P<0.001)，其表达水平与肝癌患者性别、年龄、病理分级，Child-Pugh分级、甲胎蛋白(alpha fetal protein，AFP)水平、血管侵袭等有关(均P<0.05)。生存分析结果提示miR-99a低表达是影响肝癌患者总生存率(overall survival，OS)和无病生存率(disease-free survival，DFS)的独立危险因素(均P<0.05)。共筛选出miR-99a靶基因169个，富集分析提示其主要涉及细胞周期阻滞、有丝分裂细胞周期的G1/S转换、泛素蛋白转移酶活性调节等功能，参与cGMP-PKG，HIF-1，Wnt等信号通路。结论：miR-99a在肝癌组织中表达下调，与患者生存预后密切相关，可作为一种潜在的抑癌基因抑制肝癌的发生、发展，极有潜力作为肝癌早期诊断、预后评估及靶向治疗的新靶标。
关键词：
癌症基因组图谱；肝癌；miR-99a
Expression of miR-99a in hepatocellular carcinoma and its clinical significance
CorrespondingAuthor: DING Youming Email: dingym@whu.edu.cn
DOI: 10.3978/j.issn.2095-6959.2019.11.005
Abstract
Objective: To observe the expression and clinical significance of miR-99a in primary liver cancer tissues, and explore the potential value of miR-99a in liver cancer research. Methods: The expression data of miR-99a and its clinical information were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Then the relationship between the expression of miR-99a and its clinic-pathological parameters and the prognostic value of miR-99a was analyzed. The bioinformatics analysis was applied to predict miR-99a target genes and perform the functional enrichment analysis of these genes. Results: The expression level of miR-99a in liver cancer was significantly downregulated than that in normal liver tissue (all P<0.001). Moreover, its expression level was significantly correlated with gender, age, histological grade, Child-Pugh grade, AFP, vascular invasion of HCC patients (all P<0.05), and survival analysis showed that low-expression of miR-99a was an independent risk factor for OS and DFS of HCC (all P<0.05). Bioinformatics analysis showed that the 169 target genes were associated with cell cycle arrest, G1/S transition of mitotic cell cycle, ubiquitin-protein transferase regulator activity, and mainly enriched in cGMP-PKG signaling pathway, HIF-1 signaling pathway, Wnt signaling pathway and so on. Conclusion: miR-99a is aberrantly expressed in HCC tissues and its expression might be a diagnostic biomarker, prognostic indicator and therapeutic target for HCC patients.
Keywords：
the Cancer Genome Atlas; liver cancer; miR-99a