Identification of potential pathogenic biomarkers in clear cell renal cell carcinoma

Wang,Zengzeng; Zhang,Zhihong; Zhang,Changwen; Xu,Yong

doi:10.3892/ol.2018.8398

Identification of potential pathogenic biomarkers in clear cell renal cell carcinoma

Authors:
- Zengzeng Wang
- Zhihong Zhang
- Changwen Zhang
- Yong Xu
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Affiliations: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China
Published online on: March 30, 2018 https://doi.org/10.3892/ol.2018.8398
Pages: 8491-8499
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The purpose of the present study was to screen potential pathogenic biomarkers of clear cell renal cell carcinoma (ccRCC) via microarray analysis. The mRNA and microRNA (miRNA) expression profiles of GSE96574 and GSE71302 were downloaded from the Gene Expression Omnibus (GEO) database, as well as the methylation profile of GSE61441. A total of 5 ccRCC tissue samples and 5 normal kidney tissue samples were contained in each profile of GSE96574 and GSE71302, and 46 ccRCC tissue samples and 46 normal kidney tissue samples were involved in GSE61441. The differentially expressed genes (DEGs) and the differentially expressed miRNAs (DEMs) were obtained via limma package in ccRCC tissues compared with normal kidney tissues. The Two Sample t‑test and the Beta distribution test were used to identify the differentially methylated sites (DMSs). The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to perform the Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs. The targets of the DEMs were screened with the miRWalk database, and the further combination analyses of DEGs, DEMs and DMSs were conducted. Additionally, reverse transcription PCR (RT‑PCR) and methylation‑specific PCR (MS‑PCR) were performed to detect the mRNA level and methylation status of HAPLN1. The mRNA levels of hsa‑miR‑204 and hsa‑miR‑218 were tested by RT‑PCR. A total of 2,172 DEGs, 202 DEMs and 2,172 DMSs were identified in RCC samples compared with normal samples. The DEGs were enriched in 1,015 GO terms and 69 KEGG pathways. A total of 10,601 miRNA‑gene pairs were identified in at least 5 algorithms of the miRWalk database. A total of 143 overlaps were identified between the DEGs and the differentially methylated genes. Furthermore, the DEGs were involved in 851 miRNA‑gene pairs, including 127 pairs in which the target genes were negatively associated with their corresponding DEMs and DMSs. HAPLN1 was lowly expressed and highly methylated in ccRCC tissues, while hsa‑miR‑204 and hsa‑miR‑218 were highly expressed. The results of the present study indicated that HAPLN1, hsa‑miR‑204 and hsa‑miR‑218 may be involved in the pathogenesis of ccRCC.

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