基于生物信息学分析肾透明细胞癌组织中差异过表达miRNAs及其临床意义

Bioinformatics analysis of up-regulated miRNAs in clear cell renal cell carcinoma and their clinical significance

[目的]基于生物信息学方法筛选肾透明细胞癌表达芯片中共同过表达的miRNAs,并对其下游靶基因进行GO Pathway、分子功能等预测,结合正常本底表达及患者生存分析,最终发现可作为肾透明细胞癌生物标记物的新miRNA。[方法]利用db DEMC 2.0人类癌症相关miRNA数据库、mir Path v.3、Human miRNA tissue atlas、PROGmiRV2等多种生物信息学手段进行肾透明细胞癌中miRNAs的全方位分析。[结果]db DEMC 2.0数据分析表明相对于正常组织,肾透明细胞癌组织中,分别存在上调miRNA 33个(GSE11016)、48个(GSE12105)和48个(GSE47582)。Venny分析得到13个共同上调miRNAs簇,该microRNAs簇仅在肾透明细胞癌、乳腺癌等部分癌种中高表达。mir Path v.3 GO分析进一步显示,下游靶基因可能与脂肪酸代谢、细胞周期、TGF-β信号通路、Hippo信号通路等密切相关。Human miRNA tissue atlas揭示miR-21-5p、miR-342-3p、miR15a-5p、miR-25-3p和miR-34a-5p等5个miRNAs在正常肾脏组织中显著高表达。生存分析表明只有miR-21-5p和miR-342-3p高表达与预后差显著。[结论]结合多种生物信息学手段发现,与正常组织比较,肾透明细胞癌组织中存在共同过表达miRNA簇且与脂肪酸代谢、细胞周期等信号通路密切相关;其中miR-342-3p由于高表达、预后差且未见报道而极有可能成为肾透明细胞癌新的生物标记物。

[Objective]To screen common up-regulated miRNAs in ccRCC microarrays based on bioinformatics methods,and to proceed GO pathway,molecular function enrichment predictions of downstream target genes in combination with normal background expression and patients’survival analysis of miRNAs,and finally new miRNAs biomarkers for ccRCC were obtained.[Method]The ubiquitous analysis of miRNAs in ccRCC was performed by using db DEMC 2.0,human cancer-associated miRNA database,mir Path v.3,Human miRNA tissue atlas,PROGmiRV2,and other bioinformatics approaches.[Result]db DEMC2.0 results showed that there were 33 miRNAs(GSE11016),48(GSE12105)and 48(GSE47582)miRNAs upregulated in ccRCC tissues.Venny analysis resulted in 13 common highly expressed miRNAs clusters,which were only highly expressed in certain cancers such as ccRCC and breast cancer.The mir Path v.3 GO analysis further showed that the downstream target genes may be closely related to fatty acid metabolism,cell cycle,TGF-βsignaling pathway,Hippo signaling pathway,et al.Human miRNA tissue atlas further revealed that five miRNAs,including miR-21-5 p,miR-342-3 p,miR15 a-5 p,miR-25-3 p,and miR-34 a-5 p,were highly expressed in normal kidney tissues.The survival analysis showed that only the high expression of miR-21-5 p and miR-342-3 p was significantly associated with poor prognosis.[Conclusion]A variety of bioinformatics methods have been used in this study.Compared with normal tissues,there are common over-expressed miRNA clusters in ccRCC tissues.Their target genes were closely related to fatty acid metabolism,cell cycle and other signal pathways.Among them,miR-342-3 p is highly likely to become a new biomarker of ccRCC due to its high expression,poor prognosis and unreported characteristics.