Research Paper Volume 12, Issue 5 pp 4424—4444

Discovery and validation of the prognostic value of the lncRNAs encoding snoRNAs in patients with clear cell renal cell carcinoma

Wuping Yang 1, 2, 3, 4, *, , Kenan Zhang 1, 2, 3, 4, *, , Lei Li 1, 2, 3, 4, , Kaifang Ma 1, 2, 3, 4, , Baoan Hong 1, 2, 3, 4, , Yanqing Gong 1, 2, 3, 4, , Kan Gong 1, 2, 3, 4, ,

  • 1 Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China
  • 2 Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China
  • 3 Institute of Urology, Peking University, Beijing 100034, P.R. China
  • 4 National Urological Cancer Center, Beijing 100034, P.R. China
* Equal contribution

received: October 29, 2019 ; accepted: February 25, 2020 ; published: March 3, 2020 ;

https://doi.org/10.18632/aging.102894
How to Cite

Copyright © 2020 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Some lncRNAs can encode small nucleolar RNAs (snoRNAs), called small nucleolar RNA host genes (SNHGs), which have exerted certain predictive values for the prognosis of some cancer patients. In this study, using RNA-seq and survival data in TCGA-KIRC, we examined the expression profile of 20 SNHGs and explored their prognostic values in ccRCC. Results showed that SNHG1, GAS5, SNHG3-8, SNHG11, SNHG12, SNHG15-17, SNHG20, SNHG22 and SNHG25 were significantly upregulated in ccRCC tissues compared with adjacent normal tissues. After adjustment for confounding factors, the multivariate analysis confirmed that increased SNHG3 expression was independently associated with shorter OS, while increased SNHG15 expression was an independent predictor of shorter RFS. Using the methylation data, the methylation status of 2 CpG sites (cg07807470 and cg15161854) and 2 CpG sites (cg00953154 and cg16459265) were negatively correlated with SNHG3 and SNHG15 expression, respectively. Moreover, low methylation levels of the 4 CpG sites were significantly associated with shorter OS. Furthermore, we validated the expression patterns, methylation status and prognostic value of SNHG3 and SNHG15 using clinical ccRCC samples. Taken together, SNHG3 and SNHG15 might be valuable prognostic markers in ccRCC, and DNA hypomethylation might play an important role in elevated SNHG3 and SNHG15 transcription in ccRCC.

Abbreviations

ccRCC: clear cell renal cell carcinoma; LncRNAs: Long non-coding RNAs; HIF: hypoxia-inducible factors; VHL: von Hippel-Lindau; snoRNAs: small nucleolar RNAs (snoRNAs); SNHGs: small nucleolar RNA host genes; OS: Overall Survival; RFS: Relapse-Free Survival; TCGA: The Cancer Genome Atlas.