Clinical significance of p16 INK4A and p14 ARF promoter methylation in renal cell carcinoma: a meta-analysis

// Yu Ren 1 , Li Xiao 2 , Guobin Weng 1 and Bingyi Shi 2 1 Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo 315000, People’s Republic of China 2 Department of Urologic Surgery, Chinese PLA General Hospital, The 309th Hospital of China People’s Liberation Army, Beijing 100094, People’s Republic of China Correspondence to: Guobin Weng, email: nbuurology@126.com Keywords: RCC, p16 INK4A , p14 ARF , promoter methylation, clinical significance Received: February 02, 2017      Accepted: June 02, 2017      Published: June 28, 2017 ABSTRACT The inactivation of p16 INK4A and p14 ARF via promoter methylation has been investigated in various cancers. However, the clinical effects of p16 INK4A and p14 ARF promoter methylation on renal cell carcinoma (RCC) remain to be clarified. The pooled data were calculated and summarized. Finally, an investigation of 14 eligible studies with 1231 RCC patients and 689 control patients was performed. Methylated p16 INK4A and p14 ARF were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2.77, P = 0.005; OR = 11.73, P < 0.001, respectively). Methylated p16 INK4A was significantly associated with the risk of RCC in the tissue subgroup, but not in the serum and urine subgroups. Methylated p16 INK4A was significantly associated with tumor size. We did not find that p16 INK4A promoter methylation was associated with sex, tumor grade, lymph node status, and tumor histology. Methylated p14 ARF was significantly correlated with sex and tumor histology. Three studies reported that p16 INK4A methylation was not significantly correlated with the prognosis of RCC. The results suggested that p16 INK4A and p14 ARF promoter methylation may be correlated with the carcinogenesis of RCC, and that methylated p14 ARF , especially, can be a major susceptibility gene. We also found the different clinicopathological significance of 16 INK4A and p14 ARF in RCC. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic effect of p16 INK4A and p14 ARF promoter methylation in RCC.