Liu Zhi-Guo, Su Jing, Liu Hao, Yang Xue-Jian, Yang Xue, Wei Ye, Zhu Xin-Yao, Song Yong, Zhao Xian-Cheng, Guo Hong-Lin
Department of Hospital Pharmacy, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu 223800, P.R. China.
Department of Hematology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu 223800, P.R. China.
Oncol Lett. 2022 Aug 19;24(4):351. doi: 10.3892/ol.2022.13471. eCollection 2022 Oct.
Clear cell renal cell carcinoma (ccRCC) originates from renal tubular epithelial cells and is the most common pathological renal cell carcinoma type with the worst prognosis. The relationship between the expression, prognosis and mechanism of ccRCC and the E2F family remains challenging. In the present study, RNA sequencing and clinical data of ccRCC from The Cancer Genome Atlas and two datasets, GSE36895 and GSE53757, from the Gene Expression Omnibus were used to identify the role of the E2F family in ccRCC. A total of 10 groups of tumor tissues and paired-normal tissues from patients with ccRCC were verified by reverse transcription-quantitative PCR. the expression, tumor grade and stage, prognosis and regulatory mechanism of the E2F family in ccRCC were analyzed. It was found that the expression levels of E2F1 to 4 and 6 to 8 were higher in ccRCC tissues than in normal tissues, whereas the expression level of E2F5 was lower in the former than in the latter. The expression levels of E2F1 to 8 were correlated with tumor stage and grade. Low expression of E2F1 to 5 and 7 to 8 was significantly associated with longer overall survival, disease-specific survival and progression-free survival times. The data revealed that the E2F family rarely has genetic mutations. The expression of E2F1, E2F2, E2F5, E2F7 and E2F8 was significantly correlated with DNA methylation, and E2F1 to E2F7 were significantly correlated with copy number and the data showed that the expression of E2Fs was significantly correlated with the cell cycle. The results of the present study suggested that E2F family genes may be potential targets for ccRCC molecular diagnosis and targeted therapy.
透明细胞肾细胞癌(ccRCC)起源于肾小管上皮细胞,是最常见的病理类型的肾细胞癌,预后最差。ccRCC与E2F家族的表达、预后及机制之间的关系仍具有挑战性。在本研究中,利用来自癌症基因组图谱的ccRCC的RNA测序和临床数据以及来自基因表达综合数据库的两个数据集GSE36895和GSE53757来确定E2F家族在ccRCC中的作用。通过逆转录定量PCR对总共10组ccRCC患者的肿瘤组织和配对正常组织进行了验证。分析了E2F家族在ccRCC中的表达、肿瘤分级和分期、预后及调控机制。发现ccRCC组织中E2F1至4以及6至8的表达水平高于正常组织,而前者中E2F5的表达水平低于后者。E2F1至8的表达水平与肿瘤分期和分级相关。E2F1至5以及7至8的低表达与更长的总生存期、疾病特异性生存期和无进展生存期显著相关。数据显示E2F家族很少发生基因突变。E2F1、E2F2、E2F5、E2F7和E2F8的表达与DNA甲基化显著相关,E2F1至E2F7与拷贝数显著相关,并且数据表明E2Fs的表达与细胞周期显著相关。本研究结果表明,E2F家族基因可能是ccRCC分子诊断和靶向治疗的潜在靶点。