Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact.
Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact.
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DOI：
10.18632/oncotarget.14783
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发表时间：
2017-02-28
期刊：
影响因子：
--
通讯作者：
Rogatto SR
中科院分区：
文献类型：
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作者：
Kuasne H;Barros-Filho MC;Busso-Lopes A;Marchi FA;Pinheiro M;Muñoz JJ;Scapulatempo-Neto C;Faria EF;Guimarães GC;Lopes A;Trindade-Filho JC;Domingues MA;Drigo SA;Rogatto SR
阴茎癌（PeCa）是贫穷和发展中国家的一个重要公共卫生问题，直到最近才在遗传学和表观遗传学研究方面进行了探讨。综合数据分析是识别参与癌症发生和进展的分子驱动因素的有力方法。综合分析了23例PeCa和12例非肿瘤性阴茎组织（NPT）的miRNA和mRNA表达谱。在用于微阵列的同一组样品和一组验证病例（PeCa = 36; NPT = 27）中评估了8种mirna和10种mrna的表达水平。81个mirna和2697个mrna在PeCa中被鉴定为差异表达。综合数据分析显示，255种mrna可能受68种mirna的调控。通过RT-qPCR， 8个mirna和9个转录本在PeCa中被证实改变。我们发现MMP1， MMP12和PPARG以及hsa-miR-31-5p， hsa-miR-224-5p和hsa-miR-223-3p能够以高灵敏度和特异性区分肿瘤与NPT。较高的MMP1表达比临床病理数据更能预测淋巴结转移。此外，PPARG和EGFR被强调为PeCa靶向治疗的潜在途径。基于HPV阳性的分析（23例中有7例）显示5个miRNA和13个mRNA差异表达。尽管在有限数量的病例中，与阴性病例相比，HPV阳性PeCa表现出较少的侵袭性表型。总的来说，利用mRNA和miRNA图谱的综合分析揭示了与肿瘤发生和进展相关的标志物。此外，MMP1表达水平是PeCa患者淋巴结转移的预测指标。
Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and progression. miRNA and mRNA expression profiles followed by integrative analysis were investigated in 23 PeCa and 12 non-neoplastic penile tissues (NPT). Expression levels of eight miRNAs and 10 mRNAs were evaluated in the same set of samples used for microarray and in a validation set of cases (PeCa = 36; NPT = 27). Eighty-one miRNAs and 2,697 mRNAs were identified as differentially expressed in PeCa. Integrative data analysis revealed 255 mRNAs potentially regulated by 68 miRNAs. Using RT-qPCR, eight miRNAs and nine transcripts were confirmed as altered in PeCa. We identified that MMP1, MMP12 and PPARG and hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p were able to distinguish tumors from NPT with high sensitivity and specificity. Higher MMP1 expression was detected as a better predictor of lymph node metastasis than the clinical-pathological data. In addition, PPARG and EGFR were highlighted as potential pathways for targeted therapy in PeCa. The analysis based on HPV positivity (7 of 23 cases) revealed five miRNA and 13 mRNA differentially expressed. Although in a limited number of cases, HPV positive PeCa presented less aggressive phenotype in comparison with negative cases. Overall, an integrative analysis using mRNA and miRNA profiles revealed markers related with tumor development and progression. Furthermore, MMP1 expression level was a predictive marker for lymph node metastasis in patients with PeCa.