Diagnostic and prognostic value of CEP55 in clear cell renal cell carcinoma as determined by bioinformatics analysis

Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant adult kidney tumor. Tumor recurrence and metastasis is the primary cause of cancer‑associated mortality in patients with ccRCC. Therefore, identification of efficient diagnostic and prognostic molecular markers may improve survival times. The GSE46699, GSE36895, GSE53000 and GSE53757 gene datasets were downloaded from the Gene Expression Omnibus database and contained 196 ccRCC samples and 164 adjacent normal kidney samples. Bioinformatics analysis was used to integrate the four microarray datasets to identify and analyze differentially expressed genes. Functional analysis revealed that there were 12 genes associated with cancer, based on the tumor‑associated gene database. Erb‑B2 receptor tyrosine kinase 4, centrosomal protein 55 (CEP55) and vascular endothelial growth factor A are oncogenes, all of which were associated with tumor stage, whereas only CEP55 was significantly associated with survival time as determined by Gene Expression Profiling Interactive Analysis. The mRNA expression levels of CEP55 in ccRCC samples were significantly higher than those observed in adjacent normal kidney tissues based on The Cancer Genome Atlas data and reverse transcription‑polymerase chain reaction results. The receiver operating characteristic curve analysis revealed that CEP55 may be considered a diagnostic biomarker for ccRCC with an area under the curve of >0.85 in the training and validation sets. High CEP55 expression was strongly associated with sex, histological grade, stage, T classification, N classification and M classification. Univariate and multivariate Cox proportional hazards analyses demonstrated that CEP55 expression was an independent risk factor for poor prognosis. In addition, gene set enrichment analysis indicated that high CEP55 expression was associated with immunization, cell adhesion, inflammation, the Janus kinase/signal transducer and activator of transcription signaling pathway and cell proliferation. In conclusion, CEP55 was increased in ccRCC samples, and may be considered a potential diagnostic and prognostic biomarker for ccRCC.

Figure 1.

Volcano plots of the aberrantly expressed genes between ccRCC tissues and adjacent normal kidney tissues in the four datasets. (A) GSE46699, (B) GSE36895, (C) GSE53000 and (D) GSE53757 data. Red dots represent upregulated genes defined as logFC>1.0 and adjusted P<0.05. Green dots indicate downregulated genes based on logFC<-1.0 and adjusted P<0.05. Black dots represent mRNA expression with |logFC|<1 and adjusted P>0.05. ccRCC, clear cell renal cell carcinoma; FC, fold change.

Figure 2.

LogFC heatmap of each expression microarray. The color label indicates the different logFC values. Abscissa, Gene Expression Omnibus accession number; ordinate, gene names. FC, fold change.

Figure 3.

Associations between the expression of (A) ERBB4, (B) CEP55 and (C) VEGFA, and the stage of clear cell renal cell carcinoma, as determined by Gene Expression Profiling Interactive Analysis. CEP55, centrosomal protein 55; ERBB4, Erb-B2 receptor tyrosine kinase 4; VEGFA, vascular endothelial growth factor A.

Figure 4.

Kaplan-Meier survival curve analysis. Association between three oncogenes and overall and disease-free survival of clear cell renal cell carcinoma was determined by Gene Expression Profiling Interactive Analysis. Overall survival analysis: (A) ERBB4, (B) CEP55 and (C) VEGFA. Disease-free survival analysis: (D) ERBB4, (E) CEP44 and (F) VEGFA. CEP55, centrosomal protein 55; ERBB4, Erb-B2 receptor tyrosine kinase 4; HR, hazard ratio; VEGFA, vascular endothelial growth factor A.

Figure 5.

Overexpression of CEP55 in ccRCC. (A) CEP55 mRNA was upregulated in 536 ccRCC tissues when compared with 74 adjacent normal kidney tissues according to TCGA data. (B) CEP55 mRNA expression was significantly increased in 71 paired ccRCC tissues compared with adjacent normal tissues, as determined using TCGA data. (C) Reverse transcription-polymerase chain reaction analysis of CEP55 expression in 15 paired ccRCC tissues and their adjacent normal tissues. Data are representative of three experiments. *P<0.05. CEP55, centrosomal protein 55; ccRCC, clear cell renal cell carcinoma; TCGA, The Cancer Genome Atlas.

Figure 6.

Receiver operating characteristic curves of centrosomal protein 55 in the (A) training and (B) validation sets. AUC, area under the curve.

Figure 7.

KEGG pathways associated with high CEP55 expression. (A) Natural killer cell-mediated cytotoxicity, (B) chemokine signaling pathway, (C) cell adhesion molecules CAMs, (D) cytokine-cytokine receptor interaction, (E) JAK/STAT signaling pathway and (F) cell cycle. CEP55, centrosomal protein 55; FDR, false discovery rate; KEGG, Kyoto Encyclopedia of Genes and Genomes; NES, normal enrichment score; NOM, normal.