Abstract: Epigenetic alteration of P16 ^INK4a  is conventionally thought to induce the initiation of carcinoma. However, the role of P16 ^INK4a  methylation in ovarian cancer still remains controversial. Therefore, we performed a meta-analysis to further elucidate the relationship between P16 ^INK4a  promoter methylation and ovarian cancer. A total of 24 studies, including 20 on risk, 10 on clinicopathological features, and 3 on prognosis, were included in our meta-analysis. Our results indicated that the frequency of P16 ^INK4a  methylation in cancer tissues was significantly higher than normal tissues and low malignant potential tumor tissues (odds ratio [OR] =5.01, 95% CI=1.55–16.14; OR =1.88, 95% CI=1.10–3.19, respectively), but similar to benign tissues (OR =1.18, 95% CI=0.52–2.65). Furthermore, P16 ^INK4a  promoter methylation was not strongly correlated with age, clinical stage, tumor differentiation, or histological subtype in patients with ovarian cancer. Additionally, survival analysis showed that patients with P16 ^INK4a  promoter methylation had a shorter progression-free survival in univariate and multivariate Cox regression models (hazard ratio =1.68, 95% CI=1.26–2.24; hazard ratio =1.55, 95% CI=1.15–2.08; respectively). In The Cancer Genome Atlas datasets, the methylation levels of seven out of nine CpG sites were significantly increased in the ovarian tumor tissues compared with the normal tissues. In conclusion, the present meta-analysis suggests that P16 ^INK4a  promoter methylation may be useful in distinguishing malignant cancer from healthy ovarian tissues, and it may be a potential predictive marker for prognosis in patients with ovarian cancer.
Keywords: ovarian cancer, P16 ^INK4a  promoter methylation, TCGA datasets, meta-analysis