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肾细胞癌三种病理亚型通用的6-长链非编码RNA预后特征的鉴定

Identification of a universal 6-lncRNA prognostic signature for three pathologic subtypes of renal cell carcinoma.

作者信息

Zuo Shuguang, Wang Liping, Wen Yuqing, Dai Gongpeng

机构信息

Center for Translational Medicine, Huaihe Hospital of Henan University, Kaifeng, Henan, China.

Institute of Infection and Immunity, Huaihe Hospital of Henan University, Kaifeng, Henan, China.

出版信息

J Cell Biochem. 2019 May;120(5):7375-7385. doi: 10.1002/jcb.28012. Epub 2018 Oct 30.

DOI:10.1002/jcb.28012
PMID:30378181
Abstract

Renal cell carcinoma (RCC) is the most common adult renal epithelial cancer susceptible to metastasis and patients with irresectable RCC always have a poor prognosis. Long noncoding RNAs (lncRNAs) have recently been documented as having critical roles in the etiology of RCC. Nevertheless, the prognostic significance of lncRNA-based signature for outcome prediction in patients with RCC has not been well investigated. Therefore, it is essential to identify a lncRNA-based signature for predicting RCC prognosis. In the current study, we comprehensively analyzed the RNA sequencing data of the three main pathological subtypes of RCC (kidney renal clear cell carcinoma [KIRC], kidney renal papillary cell carcinoma [KIRP], and kidney chromophobe carcinoma [KICH]) from The Cancer Genome Atlas (TCGA) database, and identified a 6-lncRNA prognostic signature with the help of a step-wise multivariate Cox regression model. The 6-lncRNA signature stratified the patients into low- and high-risk groups with significantly different prognosis. Multivariate Cox regression analysis showed that predictive value of the 6-lncRNA signature was independent of other clinical or pathological factors in the entire cohort and in each cohort of RCC subtypes. In addition, the three independent prognostic clinical factors (including age, pathologic stage III, and stage IV) was also stratified into low- and high-risk groups basis on the risk score, and the stratification analyses demonstrated that the high-risk score was a poor prognostic factor. In conclusion, these findings indicate that the 6-lncRNA signature is a novel prognostic biomarker for all three subtypes of RCC, and can increase the accuracy of predicting overall survival.

摘要

肾细胞癌(RCC)是最常见的易发生转移的成人肾上皮癌,无法切除的RCC患者预后通常较差。长链非编码RNA(lncRNA)最近被证明在RCC的病因中起关键作用。然而,基于lncRNA的特征对RCC患者预后预测的意义尚未得到充分研究。因此,确定一种基于lncRNA的特征来预测RCC预后至关重要。在本研究中,我们全面分析了来自癌症基因组图谱(TCGA)数据库的RCC三种主要病理亚型(肾透明细胞癌[KIRC]、肾乳头状细胞癌[KIRP]和肾嫌色细胞癌[KICH])的RNA测序数据,并借助逐步多变量Cox回归模型确定了一个由6个lncRNA组成的预后特征。这6个lncRNA特征将患者分为预后显著不同的低风险组和高风险组。多变量Cox回归分析表明,在整个队列以及RCC各亚型队列中,6个lncRNA特征的预测价值独立于其他临床或病理因素。此外,根据风险评分,三个独立的预后临床因素(包括年龄、病理III期和IV期)也被分为低风险组和高风险组,分层分析表明高风险评分是一个不良预后因素。总之,这些发现表明,6个lncRNA特征是RCC所有三种亚型的一种新型预后生物标志物,可提高预测总生存期的准确性。

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