Department of Urology, Ningbo Medical Centre Lihuili Hospital, Ningbo, Zhejiang 315040, P.R. China.
Department of Urology, Cancer Hospital of China Medical University, Shenyang, Liaoning 110042, P.R. China.
Mol Med Rep. 2019 May;19(5):3485-3496. doi: 10.3892/mmr.2019.10042. Epub 2019 Mar 15.
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.
透明细胞肾细胞癌（ccRCC）是成人最常见的恶性肾肿瘤之一。肿瘤复发和转移是 ccRCC 患者癌症相关死亡的主要原因。因此，鉴定有效的诊断和预后分子标志物可能会提高患者的生存时间。从基因表达综合数据库中下载 GSE46699、GSE36895、GSE53000 和 GSE53757 基因数据集，包含 196 个 ccRCC 样本和 164 个相邻正常肾样本。通过生物信息学分析整合这四个微阵列数据集，以识别和分析差异表达基因。功能分析表明，基于肿瘤相关基因数据库，有 12 个基因与癌症相关。表皮生长因子受体-2 受体酪氨酸激酶 4、中心体蛋白 55（CEP55）和血管内皮生长因子 A 是致癌基因，均与肿瘤分期有关，而只有 CEP55 与基因表达谱交互分析确定的生存时间显著相关。根据癌症基因组图谱数据和逆转录-聚合酶链反应结果，ccRCC 样本中 CEP55 的 mRNA 表达水平明显高于相邻正常肾组织。受试者工作特征曲线分析表明，CEP55 可能是 ccRCC 的诊断生物标志物，在训练集和验证集中曲线下面积均大于 0.85。CEP55 高表达与性别、组织学分级、分期、T 分类、N 分类和 M 分类密切相关。单因素和多因素 Cox 比例风险分析表明，CEP55 表达是预后不良的独立危险因素。此外，基因集富集分析表明，CEP55 高表达与免疫、细胞黏附、炎症、Janus 激酶/信号转导和转录激活因子信号通路以及细胞增殖有关。总之，ccRCC 样本中 CEP55 表达增加，可能是 ccRCC 的潜在诊断和预后生物标志物。
