Quantitative assessment of aberrant <em>P16^INK4a</em> methylation in ovarian cancer: a meta-analysis based on literature and TCGA datasets

Abstract

Epigenetic alteration of P16INK4a is conventionally thought to induce the initiation of carcinoma. However, the role of P16INK4a methylation in ovarian cancer still remains controversial. Therefore, we performed a meta-analysis to further elucidate the relationship between P16INK4a 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 P16INK4a 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, P16INK4a 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 P16INK4a 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 P16INK4a 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.

<p>Identification of High-Frequency Methylation Sites in RNF180 Promoter Region Affecting Expression and Their Relationship with Prognosis of Gastric Cancer</p>

“…30 For the above reasons, hypermethylation of tumor suppressor genes can lead to poor prognosis for tumor patients. 31 In order to analyze the methylation and prognosis, we analyzed the relationship between the methylation rate of the above five sites and the prognosis of GC. The results showed that the methylation rate of M5(−148) (Chr5:64,165,959) and M27(−26)(Chr5:64,166,081) could indicate poor prognosis by setting a cut-off value of 0.3.…”

Indole Derivative Interacts with Estrogen Receptor Beta and Inhibits Human Ovarian Cancer Cell Growth

“…Interestingly, other authors have suggested that aberrant methylation of CDKN2A promoter may be essential to the initiation of ovarian cancer and in distinguishing malignant from healthy ovarian tissues. Besides, CDKN2A promoter methylation is a potential predictive factor for poor prognosis in ovarian cancer [ 40 ].…”

Differential Expression of Potential Biomarkers of Oral Squamous Cell Carcinoma Development

“…Different proteins, depending on their upregulated or downregulated status, can participate in the process of cancer development progression in addition to affecting tumor behavior and aggressiveness [10]. Thus, based on the promising biomarkers published, we selected certain targets such as: survivin and BCL2 apoptosis regulator (BCL2) that support cell division and anti-apoptotic function [11,12]; cyclin dependent kinase inhibitor 2A (CDKN2A) that regulates the progression from the G1 to the S phase in the cell cycle, the polo like kinase 1 (PLK1) that regulates the G2/M transition [13,14]; epidermal growth factor receptor (EGFR) that promotes cell survival and proliferation [15]; and nuclear cyclin D1 (CCND1) that, when accumulated, results in an aberrant increase in cell proliferation activity [16]. The main function of p63 is to maintain the proliferative potential of progenitor epidermal cells, predominantly located in basal layers.…”