Qin Shijie, Shi Xuejia, Wang Canbiao, Jin Ping, Ma Fei
Laboratory for Comparative Genomics and Bioinformatics, College of Life Science, Nanjing Normal University, Nanjing 210046, China.
Cancers (Basel). 2019 Oct 28;11(11):1668. doi: 10.3390/cancers11111668.
Clear cell renal cell carcinoma (ccRCC) still remains a higher mortality rate in worldwide. Obtaining promising biomakers is very crucial for improving the diagnosis and prognosis of ccRCC patients. Herein, we firstly identified eight potentially prognostic miRNAs (hsa-miR-144-5p, hsa-miR-223-3p, hsa-miR-365b-3p, hsa-miR-3613-5p, hsa-miR-9-5p, hsa-miR-183-5p, hsa-miR-335-3p, hsa-miR-1269a). Secondly, we found that a signature containing these eight miRNAs showed obviously superior to a single miRNA in the prognostic effect and credibility for predicting the survival of ccRCC patients. Thirdly, we discovered that twenty-two transcription factors (TFs) interact with these eight miRNAs, and a signature combining nine TFs (, , , , , , , , and ) could promote the prognosis of ccRCC patients. Finally, we further identified eleven genes (hsa-miR-365b-3p, hsa-miR-223-3p, hsa-miR-1269a, hsa-miR-144-5p, hsa-miR-183-5p, hsa-miR-335-3p, , , , , ) that could combine as a signature to improve the prognosis effect of ccRCC patients, which distinctly outperformed the eight-miRNA signature and the nine-TF signature. Overall, we identified several new prognosis factors for ccRCC, and revealed a potential mechanism that TFs and miRNAs interplay cooperatively or oppositely regulate a certain number of tumor suppressors, driver genes, and oncogenes to facilitate the survival of ccRCC patients.
透明细胞肾细胞癌(ccRCC)在全球范围内的死亡率仍然较高。获得有前景的生物标志物对于改善ccRCC患者的诊断和预后至关重要。在此,我们首先鉴定出八个潜在的预后性微小RNA(hsa-miR-144-5p、hsa-miR-223-3p、hsa-miR-365b-3p、hsa-miR-3613-5p、hsa-miR-9-5p、hsa-miR-183-5p、hsa-miR-335-3p、hsa-miR-1269a)。其次,我们发现包含这八个微小RNA的特征在预测ccRCC患者生存的预后效果和可信度方面明显优于单个微小RNA。第三,我们发现二十二个转录因子(TFs)与这八个微小RNA相互作用,并且一个结合九个TFs(,,,,,,,,和)的特征可以改善ccRCC患者的预后。最后,我们进一步鉴定出十一个基因(hsa-miR-365b-3p、hsa-miR-223-3p、hsa-miR-1269a、hsa-miR-144-5p、hsa-miR-183-5p、hsa-miR-335-3p、,,,,),它们可以组合成一个特征以改善ccRCC患者的预后效果,这明显优于八个微小RNA特征和九个TF特征。总体而言,我们鉴定出了几个新的ccRCC预后因素,并揭示了一种潜在机制,即TFs和微小RNA协同或相反地相互作用,调节一定数量的肿瘤抑制基因、驱动基因和癌基因,以促进ccRCC患者的生存。