Meta-Analysis:

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. We therefore performed a meta-analysis to further elucidate the relationship between P16^INK4a 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 (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 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 methylation had a shorter progression-free survival in univariate and multivariate Cox regression models (HR = 1.68, 95% CI = 1.26-2.24; HR = 1.55, 95% CI = 1.15-2.08; respectively). P16^INK4a methylation was also linked to an unfavorable overall survival, although the correlation was not statistically significant. In conclusion, the present meta-analysis suggests that P16^INK4a 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.