Li Ming, Wang Ying, Song Yongsheng, Bu Renge, Yin Bo, Fei Xiang, Guo Qizhen, Wu Bin
Department of Urology, Shengjing Hospital of China Medical University Shenyang, Liaoning 110004, P. R. China ; Department of Cell Biology, Harvard Medical School Boston 02115, USA.
Department of Nuclear Medicine, The First Affiliated Hospital of China Medical University Shenyang, Liaoning 110001, P. R. China.
Int J Clin Exp Pathol. 2014 Oct 15;7(11):7597-609. eCollection 2014.
This study aimed to evaluate the expression of DNA methyltransferase (DNMT) family proteins in renal cell carcinoma (RCC) and to assess the clinical significance and prognostic value of their expression patterns.
A total of 97 renal cell carcinoma and 52 no-tumor tissues were recruited for immunohistochemical analysis of their expression.
DNMT1, DNMT3A and DNMT3B proteins were highly expressed in clear cell RCC, papillary RCC and chromophobe RCC tissues than that of no-tumor tissues (all P < 0.05). DNMT1, DNMT3A and DNMT3B expression was significantly associated with tumor size (P=0.003, 0.001 and 0.003, respectively), tumor pathology stage (P=0.039, 0.034 and 0.037, respectively), histopathological grading (P=0.042, 0.026 and 0.031, respectively), lymph node metastasis (P=0.022, 0.030 and 0.020, respectively) and vascular invasion (P=0.042, 0.031 and 0.044, respectively). The Kaplan-Meier survival analysis demonstrated that expression of DNMTs protein in RCC was significantly associated with shorter over all survival and disease-free survival (all P < 0.05). Furthermore, multivariate analysis showed that the expression of DNMT1 was an independent prognostic factor for overall survival (OS) (P=0.036), and the expression of DNMT3A or DNMT3B was an independent prognostic factor for disease-free survival (DFS) in the patients (P=0.031 and P=0.023, respectively).
DNMTs were higher expressed in RCC than no-tumor tissues, and the expression of DNMTs were strongly associated with RCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence, and prognosis. DNMTs may thus serve as prognostic markers and novel therapeutic targets for RCC patients.
本研究旨在评估DNA甲基转移酶（DNMT）家族蛋白在肾细胞癌（RCC）中的表达情况，并评估其表达模式的临床意义和预后价值。
共纳入97例肾细胞癌组织和52例非肿瘤组织进行免疫组化分析，以检测其表达情况。
与非肿瘤组织相比，DNMT1、DNMT3A和DNMT3B蛋白在透明细胞RCC、乳头状RCC和嫌色细胞RCC组织中高表达（所有P<0.05）。DNMT1、DNMT3A和DNMT3B的表达与肿瘤大小（分别为P=0.003、0.001和0.003）、肿瘤病理分期（分别为P=0.039、0.034和0.037）、组织病理学分级（分别为P=0.042、0.026和0.031）、淋巴结转移（分别为P=0.022、0.030和0.020）以及血管侵犯（分别为P=0.042、0.031和0.044）显著相关。Kaplan-Meier生存分析表明，RCC中DNMTs蛋白的表达与总体生存期和无病生存期缩短显著相关（所有P<0.05）。此外，多因素分析显示，DNMT1的表达是总体生存期（OS）的独立预后因素（P=0.036），DNMT3A或DNMT3B的表达是患者无病生存期（DFS）的独立预后因素（分别为P=0.031和P=0.023））。
DNMTs在RCC中的表达高于非肿瘤组织，且其表达与RCC的肿瘤大小、肿瘤病理分期、组织学分级、淋巴结转移、血管侵犯以及复发和预后密切相关。因此，DNMTs可能作为RCC患者的预后标志物和新的治疗靶点。
