Research Papers:
An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients
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Abstract
Ping-Ying Chang1,2, Yu-Ping Liao3, Hui-Chen Wang3, Yu-Chih Chen4, Rui-Lan Huang5, Yu-Chi Wang6, Chiou-Chung Yuan5 and Hung-Cheng Lai1,3,5,7,8,9
1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Republic of China
2Division of Hematology & Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Republic of China
3Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Republic of China
4Division of Research and Analysis, Food and Drug Administration, Ministry of Health and Welfare, Taipei, Republic of China
5Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Republic of China
6Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Republic of China
7Translational Epigenetic Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Republic of China
8Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China
9Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China
Correspondence to:
Hung-Cheng Lai, email: [email protected], [email protected]
Keywords: ovarian cancer, DNA methylation, adhesion, prognosis
Received: January 30, 2017 Accepted: May 10, 2017 Published: June 16, 2017
ABSTRACT
DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival. Low methylation of VTN was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of CTNNA1, DLC1 or MFAP4 were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs.
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