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

Wuping Yang,Kenan Zhang,Yanqing Gong,Lei Li,Kan Gong,Kaifang Ma,Baoan Hong

doi:10.18632/aging.102894

Wuping Yang, Kenan Zhang + Show 5 more

Open Access

https://doi.org/10.18632/aging.102894

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Journal: Aging	Publication Date: Mar 3, 2020
Citations: 28	License type: cc-by

Affiliation: Peking University First Hospital, Peking University

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.

Highlights

Renal cell carcinoma (RCC) is one of the most aggressive cancers of the urinary system, accounting for approximately 4% of adult malignancies [1]
Using RNA-seq data in the Cancer Genome Atlas (TCGA)-Kidney Renal Clear Cell Carcinoma (KIRC), we compared the expression of long non-coding RNAs (ncRNAs) (lncRNAs) encoding small nucleolar RNAs (snoRNAs) between clear cell RCC (ccRCC) tissues and the matched adjacent normal tissues
Results showed that compared with adjacent normal tissues, SNHG1, GAS5, SNHG3-8, SNHG11, SNHG12, SNHG15-17, SNHG20, SNHG22 and SNHG25 were significantly upregulated in ccRCC tissues, while SNHG9, SNHG10, DANCR and SNHG14 were remarkably downregulated in ccRCC tissues (Figure 2A–2C)

Summary

INTRODUCTION

Renal cell carcinoma (RCC) is one of the most aggressive cancers of the urinary system, accounting for approximately 4% of adult malignancies [1]. The most common histologic subtype clear cell RCC (ccRCC) accounts for approximately 75-80% of RCC, and up to 92% of these cancers have VHL protein inactivation [2,3,4]. Emerging studies indicate that lncRNAs are differentially expressed in ccRCC and exert critical regulatory effects on a series of cellular processes, such as proliferation, apoptosis and metastasis [11, 12]. The SNHGs, as the host genes of snoRNAs, may have multiple regulatory effects on tumor cell processes and play crucial roles in cancer. In this study, using RNA-seq and survival data in the Cancer Genome Atlas (TCGA)-Kidney Renal Clear Cell Carcinoma (KIRC), we examined the expression profile of some SNHGs and explored their prognostic values in ccRCC, followed by validation in a certain number of paired clinical samples (adjacent normal renal tissue and ccRCC)

RESULTS

DISCUSSION

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