hsa-mir-3199-2 and hsa-mir-1293 as Novel Prognostic Biomarkers of Papillary Renal Cell Carcinoma by COX Ratio Risk Regression Model Screening
hsa-mir-3199-2 and hsa-mir-1293 as Novel Prognostic Biomarkers of Papillary Renal Cell Carcinoma by COX Ratio Risk Regression Model Screening
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DOI：
10.1002/jcb.26008
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发表时间：
2017-10-01
影响因子：
4
通讯作者：
Wang, Xiu-Xin
中科院分区：
文献类型：
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作者：
Luo, Wen;Wang, Lei;Wang, Xiu-Xin
乳头状肾细胞癌（PRCC）是第二常见和侵袭性的肾细胞癌。鉴定新的microRNA生物标志物可能有助于PRCC患者的诊断和预后。我们的目的是筛选可以作为预后因素和预测PRCC患者生存的差异表达的mirna。从TCGA （The Cancer Genome Atlas）数据集中下载274份PRCC样本的高通量mirna数据，并鉴定出感兴趣的mirna。对这些mirna进行了层次聚类和主成分分析（PCA）。LASSO筛选可作为预后因素的关键基因。并采用Kaplan-Meier生存分析和ROC （Receiver Operating Characteristic）生长曲线验证模型的准确性。通过GO （GO Ontology）和KEGG （Kyoto Encyclopedia of Genes and Genomes）等生物信息学方法分析miRNAs的可能靶点的生物学过程。与健康对照相比，在PRCC样本中共筛选出105个差异表达的mirna。两个关键mirna， hsa-mir-3199-2和hsa-mir-1293，通过LASSO（最小绝对收缩和选择算子）筛选出来，分别包括197和189个靶基因。通过ROC分析，其曲线下面积（AUC）分别为0.7774968和0.6743466，验证了其准确性。这些mirna在血小板活化因子生物合成过程、上皮细胞成熟和IkappaB激酶复合物等途径中显著富集。综上所述，筛选出可作为PRCC预后生物标志物的hsa-mir-3199-2和hsa-mir-1293，可为该疾病的临床治疗提供新的见解。(C) 2017 Wiley期刊公司
Papillary renal cell carcinoma(PRCC) is the second most common and aggressive renal cell carcinoma. Identification of novel microRNA biomarkers could be beneficial for the diagnosis and prognosis of PRCC patients. We aimed to screen differentially expressed miRNAs that can act as prognostic factors and to predict the survival of PRCC patients. High-throughput data of miRNAs of 274 PRCC samples were downloaded from TCGA (The Cancer Genome Atlas) dataset and interested miRNAs were identified. Hierarchical clustering and principal component analysis (PCA) were performed on these miRNAs. Critical genes that can act as prognostic factors were screened by LASSO. What's more, Kaplan-Meier survival analysis and ROC (Receiver Operating Characteristic) growth curve were used to testify the accuracy of the model. Biological processes of putative targets of miRNAs were analyzed by bioinformatics methods such as GO (Go Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. A total of 105 differentially expressed miRNAs were screened out in PRCC samples compared with healthy controls. Two critical miRNAs, hsa-mir-3199-2, and hsa-mir-1293, were screened out by LASSO (Least Absolute Shrinkage and Selection Operator), including 197 and 189 target genes, respectively. Furthermore, its' accuracy was testified by ROC analysis with the AUC (Area under the curve) value of 0.7774968 and 0.6743466. These miRNAs were significantly enriched in pathways as platelet activating factor biosynthetic process, epithelial cell maturation, and IkappaB kinase complex. In conclusion, hsa-mir-3199-2 and hsa-mir-1293 that can act as prognostic biomarkers of PRCC were screened out, which can provide new insights for the clinical treatment of the disease. (C) 2017 Wiley Periodicals, Inc.