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通过COX比例风险回归模型筛选,hsa - mir - 3199 - 2和hsa - mir - 1293作为乳头状肾细胞癌新的预后生物标志物

hsa-mir-3199-2 and hsa-mir-1293 as Novel Prognostic Biomarkers of Papillary Renal Cell Carcinoma by COX Ratio Risk Regression Model Screening.

作者信息

Luo Wen, Wang Lei, Luo Mao-Hua, Huang Yu-Zhu, Yang Hua, Zhou Yu, Jia Hong-Tao, Wang Xiu-Xin

机构信息

Department of Urological Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.

Department of Urology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, China.

出版信息

J Cell Biochem. 2017 Oct;118(10):3488-3494. doi: 10.1002/jcb.26008. Epub 2017 May 30.

Abstract

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. J. Cell. Biochem. 118: 3488-3494, 2017. © 2017 Wiley Periodicals, Inc.

摘要

乳头状肾细胞癌(PRCC)是第二常见且侵袭性较强的肾细胞癌。鉴定新的微小RNA生物标志物可能有助于PRCC患者的诊断和预后评估。我们旨在筛选可作为预后因素的差异表达微小RNA,并预测PRCC患者的生存情况。从癌症基因组图谱(TCGA)数据集下载了274例PRCC样本的微小RNA高通量数据,并鉴定出感兴趣的微小RNA。对这些微小RNA进行了层次聚类和主成分分析(PCA)。通过套索(LASSO)筛选出可作为预后因素的关键基因。此外,使用Kaplan-Meier生存分析和ROC(受试者工作特征)生长曲线来验证模型的准确性。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析等生物信息学方法分析了微小RNA假定靶标的生物学过程。与健康对照相比,在PRCC样本中总共筛选出105个差异表达的微小RNA。通过套索(LASSO,最小绝对收缩和选择算子)筛选出两个关键的微小RNA,即hsa-mir-3199-2和hsa-mir-1293,分别包括197个和189个靶基因。此外,通过ROC分析验证了其准确性,曲线下面积(AUC)值分别为0.7774968和0.6743466。这些微小RNA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。总之,筛选出了可作为PRCC预后生物标志物的hsa-mir-3199-2和hsa-mir-1293,这可为该疾病的临床治疗提供新的见解。《细胞生物化学杂志》118:3488 - 3494,2017年。©2017威利期刊公司

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