Clinical significance of p16INK4A and p14ARF promoter methylation in renal cell carcinoma: a meta-analysis

Yu Ren, Li Xiao, Guobin Weng _ and Bingyi Shi

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Oncotarget. 2017; 8:64385-64394. https://doi.org/10.18632/oncotarget.18826

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Yu Ren1, Li Xiao2, Guobin Weng1 and Bingyi Shi2

1Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo 315000, People’s Republic of China

2Department 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: [email protected]

Keywords: RCC, p16INK4A, p14ARF, promoter methylation, clinical significance

Received: February 02, 2017     Accepted: June 02, 2017     Published: June 28, 2017


The inactivation of p16INK4A and p14ARF via promoter methylation has been investigated in various cancers. However, the clinical effects of p16INK4A and p14ARF 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 p16INK4A and p14ARF 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 p16INK4A was significantly associated with the risk of RCC in the tissue subgroup, but not in the serum and urine subgroups. Methylated p16INK4A was significantly associated with tumor size. We did not find that p16INK4A promoter methylation was associated with sex, tumor grade, lymph node status, and tumor histology. Methylated p14ARF was significantly correlated with sex and tumor histology. Three studies reported that p16INK4A methylation was not significantly correlated with the prognosis of RCC. The results suggested that p16INK4A and p14ARF promoter methylation may be correlated with the carcinogenesis of RCC, and that methylated p14ARF, especially, can be a major susceptibility gene. We also found the different clinicopathological significance of 16INK4A and p14ARF in RCC. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic effect of p16INK4A and p14ARF promoter methylation in RCC.

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