Next Article in Journal
Rhein Induces Oxidative Stress and Apoptosis in Mouse Blastocysts and Has Immunotoxic Effects during Embryonic Development
Previous Article in Journal
Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms
Previous Article in Special Issue
Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(9), 2017; doi:10.3390/ijms18092017

Comprehensive Evaluation of TFF3 Promoter Hypomethylation and Molecular Biomarker Potential for Prostate Cancer Diagnosis and Prognosis

1
Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark
2
Department of Histopathology, Aarhus University Hospital, 8200 Aarhus N, Denmark
3
Department of Urology, Aarhus University Hospital, 8200 Aarhus N, Denmark
4
Department of Clinical Genetics, Aarhus University Hospital, 8200 Aarhus N, Denmark
5
Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 25 August 2017 / Revised: 8 September 2017 / Accepted: 13 September 2017 / Published: 20 September 2017
(This article belongs to the Special Issue Cancer Epigenetics)
View Full-Text   |   Download PDF [970 KB, uploaded 21 September 2017]   |  

Abstract

Overdiagnosis and overtreatment of clinically insignificant tumors remains a major problem in prostate cancer (PC) due to suboptimal diagnostic and prognostic tools. Thus, novel biomarkers are urgently needed. In this study, we investigated the biomarker potential of Trefoil factor 3 (TFF3) promoter methylation and RNA expression levels for PC. Initially, by quantitative methylation specific PCR (qMSP) analysis of a large radical prostatectomy (RP) cohort (n = 292), we found that the TFF3 promoter was significantly hypomethylated in PC compared to non-malignant (NM) prostate tissue samples (p < 0.001) with an AUC (area under the curve) of 0.908 by receiver operating characteristics (ROC) curve analysis. Moreover, significant TFF3 promoter hypomethylation (p ≤ 0.010) as well as overexpression (p < 0.001) was found in PC samples from another large independent patient sample set (498 PC vs. 67 NM) analyzed by Illumina 450K DNA methylation arrays and/or RNA sequencing. TFF3 promoter methylation and transcriptional expression levels were inversely correlated, suggesting that epigenetic mechanisms contribute to the regulation of gene activity. Furthermore, low TFF3 expression was significantly associated with high ERG, ETS transcription factor (ERG) expression (p < 0.001), as well as with high Gleason score (p < 0.001), advanced pathological T-stage (p < 0.001), and prostate-specific antigen (PSA) recurrence after RP (p = 0.013; univariate Cox regression analysis). There were no significant associations between TFF3 promoter methylation levels, ERG status, or PSA recurrence in these RP cohorts. In conclusion, our results demonstrated diagnostic biomarker potential of TFF3 promoter hypomethylation for PC as well as prognostic biomarker potential of TFF3 RNA expression. To the best of our knowledge, this is the most comprehensive study of TFF3 promoter methylation and transcriptional expression in PC to date. View Full-Text
Keywords: prostate cancer; DNA methylation; expression; TFF3; biomarker; diagnosis; prognosis prostate cancer; DNA methylation; expression; TFF3; biomarker; diagnosis; prognosis
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Nørgaard, M.; Haldrup, C.; Storebjerg, T.M.; Vestergaard, E.M.; Wild, P.J.; Høyer, S.; Borre, M.; Ørntoft, T.F.; Sørensen, K.D. Comprehensive Evaluation of TFF3 Promoter Hypomethylation and Molecular Biomarker Potential for Prostate Cancer Diagnosis and Prognosis. Int. J. Mol. Sci. 2017, 18, 2017.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top