J Cancer 2020; 11(14):4274-4283. doi:10.7150/jca.40421

Research Paper

A Panel of Four-lncRNA Signature as a Potential Biomarker for Predicting Survival in Clear Cell Renal Cell Carcinoma

Haoran Liu1,2#, Tao Ye1,2#, Xiaoqi Yang1,2, Peng Lv1,2, Xiaoliang Wu1,2, Hui Zhou1,2, Jin Zeng1,2, Kun Tang1,2,✉, Zhangqun Ye1,2

1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2. Hubei Institute of Urology, Wuhan 430030, China
# Haoran Liu and Tao Ye contributed equally to this work.

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Citation:
Liu H, Ye T, Yang X, Lv P, Wu X, Zhou H, Zeng J, Tang K, Ye Z. A Panel of Four-lncRNA Signature as a Potential Biomarker for Predicting Survival in Clear Cell Renal Cell Carcinoma. J Cancer 2020; 11(14):4274-4283. doi:10.7150/jca.40421. Available from http://www.jcancer.org/v11p4274.htm

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Abstract

Long non-coding RNAs (lncRNAs) have been considered as biomarkers for the carcinogenesis and development of various cancers. However, the prognostic significance of lncRNAs in renal cell carcinoma (RCC) remains unclear. This study aimed to determine the predictive ability of lncRNAs in clear cell RCC (ccRCC). Among the cohort of kidney renal clear cell carcinoma (KIRC) of the The Cancer Genome Atlas (TCGA), 525 patients were enrolled in our study. Expression of lncRNAs based on RNAseq was obtained from TCGA. Kaplan-Meier prognostic analysis and a Cox proportional hazards regression model were used to assess related factors. The lncRNA signature was then validated in an independent cohort of an additional 60 ccRCC patients. Hierarchical clustering of the KIRC TCGA dataset identified 26 differentially expressed lncRNAs (11 down-regulated and 15 up-regulated) using average linkage clustering. Kaplan-Meier survival analysis identified 30 statistically significant lncRNAs that strongly predicted prognosis, with 4 ccRCC-specific lncRNAs (TCL6, PVT1, MIR155HG, and HAR1B) being differentially expressed and correlating significantly with OS. Patients assigned to the high-risk group were associated with poor OS compared with patients in the low-risk group (HR = 2.57; 95%CI, 1.89-3.50; p < 0.001). This finding was validated in the Tongji Hospital cohort, and the four-lncRNA signature was shown to be significantly predictive of ccRCC prognosis (p < 0.001). In this study, we constructed an applicable four-lncRNA-based classifier as a reliable prognostic and predictive tool for OS in patients with ccRCC.

Keywords: lncRNAs, Prognosis, Survival, Clear Cell Renal Cell Carcinoma