Shen Tao, Song Yingdong, Wang Xiangting, Wang Haiyang
Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, Key Laboratory of Biomedicine in Gene Diseases, Health of Anhui Higher Education Institutes, College of Life Sciences, Anhui Normal University, Wuhu, China.
Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
Front Mol Biosci. 2022 Aug 26;9:967934. doi: 10.3389/fmolb.2022.967934. eCollection 2022.
Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease that is associated with poor prognosis. Recent works have revealed the significant roles of miRNA in ccRCC initiation and progression. Comprehensive characterization of ccRCC based on the prognostic miRNAs would contribute to clinicians' early detection and targeted treatment. Here, we performed unsupervised clustering using TCGA-retrieved prognostic miRNAs expression profiles. Two ccRCC subtypes were identified after assessing principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and consensus heatmaps. We found that the two subtypes are associated with distinct clinical features, overall survivals, and molecular characteristics. C1 cluster enriched patients in relatively early stage and have better prognosis while patients in C2 cluster have poor prognosis with relatively advanced state. Mechanistically, we found the differentially expressed genes (DEGs) between the indicated subgroups dominantly enriched in biological processes related to transmembrane transport activity. In addition, we also revealed a miRNA-centered DEGs regulatory network, which severed as essential regulators in both transmembrane transport activity control and ccRCC progression. Together, our work described the molecular heterogeneity among ccRCC cancers, provided potential targets served as effective biomarkers for ccRCC diagnosis and prognosis, and paved avenues to better understand miRNA-directed regulatory network in ccRCC progression.
透明细胞肾细胞癌（ccRCC）是一种异质性疾病，预后较差。最近的研究揭示了miRNA在ccRCC发生和发展中的重要作用。基于预后性miRNA对ccRCC进行全面表征将有助于临床医生进行早期检测和靶向治疗。在此，我们使用从TCGA获取的预后性miRNA表达谱进行了无监督聚类。在评估主成分分析（PCA）、t分布随机邻域嵌入（t-SNE）和一致性热图后，鉴定出两种ccRCC亚型。我们发现这两种亚型与不同的临床特征、总生存期和分子特征相关。C1簇富集相对早期的患者，预后较好，而C2簇的患者预后较差，处于相对晚期状态。从机制上讲，我们发现指定亚组之间的差异表达基因（DEG）主要富集在与跨膜转运活性相关的生物学过程中。此外，我们还揭示了一个以miRNA为中心的DEG调控网络，该网络在跨膜转运活性控制和ccRCC进展中均作为关键调节因子。总之，我们的工作描述了ccRCC癌症之间的分子异质性，提供了作为ccRCC诊断和预后有效生物标志物的潜在靶点，并为更好地理解ccRCC进展中miRNA导向的调控网络铺平了道路。
