Abstract
Clear cell renal cell carcinoma (ccRCC) is a fatal cancer of the urinary system. Long non-coding RNAs (lncRNAs) act as competitive endogenous RNAs (ceRNAs) involving the ccRCC progression. However, the relationship between the ceRNA network and immune signature is largely unknown. In this study, the ccRCC-related gene expression profiles retrieved from the TCGA database were used first to identify the differentially expressed genes through differential gene expression analysis and weighted gene co-expression network analysis. The interaction among differentially expressed lncRNAs, miRNAs, and mRNAs were matched using public databases. As a result, a ceRNA network was developed that contained 144 lncRNAs, 23 miRNAs, as well as 62 mRNAs. Four of 144 lncRNAs including LINC00943, SRD5A3-AS1, LINC02345, and U62317.3 were identified through LASSO regression and Cox regression analyses, and were used to create a prognostic risk model. Then, the ccRCC samples were divided into the high- and low-risk groups depending on their risk scores. ROC curves, Kaplan-Meier survival analysis, and the survival risk plots indicated that the predictive performance of our developed risk model was accurate. Moreover, the CIBERSORT algorithm was used to measure the infiltration levels of immune cells in the ccRCC samples. The further genomic analysis illustrated a positive correlation between most immune checkpoint blockade-related genes and the risk score. In conclusion, the present findings effectually contribute to the comprehensive understanding of the ccRCC pathogenesis, and may offer a reference for developing novel therapeutic and prognostic biomarkers.
Highlights
Renal cell carcinoma (RCC) has been known to be among the most fatal cancers in the urinary system [1]
In order to detect the differentially expressed Long non-coding RNAs (lncRNAs), miRNAs, and messenger RNAs (mRNAs), the The Cancer Genome Atlas (TCGA) database was searched for the RNA sequencing data of Clear cell renal cell carcinoma (ccRCC) samples
LncRNA SARCC expression in ccRCC tissues decreases, and low SARCC expression is associated with a worse prognosis
Summary
Renal cell carcinoma (RCC) has been known to be among the most fatal cancers in the urinary system [1]. RCC consists of three major histological subtypes, including chromophobe RCC, papillary RCC, and clear cell renal cell carcinoma (ccRCC). CcRCC is reported to be responsible for ~ 80% of total RCC incidence [2, 3]. Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) with a length of >200 nucleotides, and exert fundamental contributions to a variety of biological processes, such as chromatin organization, transcriptional regulation, and posttranscriptional modification [7]. The competitive endogenous RNA (ceRNA) concept describes the function of lncRNAs, messenger RNAs (mRNAs), and other RNA transcript types as natural miRNA “sponges” that suppress miRNA functions via miRNA response elements (MREs) [9]. Several studies have validated the ceRNA hypothesis, and it is widely recognized as tightly associated with the initiation and progression of various cancers [10, 11]
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