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Quantitative assessment of aberrant P16INK4a methylation in ovarian cancer: a meta-analysis based on literature and TCGA datasets

Authors Ruan J, Xu P, Fan W, Deng Q, Yu M

Received 11 April 2018

Accepted for publication 14 June 2018

Published 29 August 2018 Volume 2018:10 Pages 3033—3046


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Professor Harikrishna Nakshatri

Jie Ruan,1,* Peipei Xu,2,3,* Wei Fan,4 Qiaoling Deng,3 Mingxia Yu3

1Key Laboratory for Medical Molecular Diagnostics of Guangdong, Guangdong Medical University, Dongguan, Guangdong, 523808, China; 2Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450072, China; 3Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China; 4Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China

*These authors contributed equally to this work

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.

Keywords: ovarian cancer, P16INK4a promoter methylation, TCGA datasets, meta-analysis

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