Expression profiling and clinicopathological significance of DNA methyltransferase 1, 3A and 3B in sporadic human renal cell carcinoma

Purpose: 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. Methods: A total of 97 renal cell carcinoma and 52 no-tumor tissues were recruited for immunohistochemical analysis of their expression. Results: 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). Conclusions: 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.