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Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in high-risk prostate cancer.
- Source :
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Journal of Cancer Research & Clinical Oncology . Nov2014, Vol. 140 Issue 11, p1849-1861. 13p. - Publication Year :
- 2014
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Abstract
- Purpose: To explore differential methylation of HAAO, HOXD3, LGALS3, PITX2, RASSF1 and TDRD1 as a molecular tool to predict biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa). Methods: A multiplexed nested methylation-specific PCR was applied to quantify promoter methylation of the selected markers in five cell lines, 42 benign prostatic hyperplasia (BPH) and 71 high-risk PCa tumor samples. Uni- and multivariate Cox regression models were used to assess the importance of the methylation level in predicting BCR. Results: A PCa-specific methylation marker HAAO in combination with HOXD3 and a hypomethylation marker TDRD1 distinguished PCa samples (>90 % of tumor cells each) from BPH with a sensitivity of 0.99 and a specificity of 0.95. High methylation of PITX2, HOXD3 and RASSF1, as well as low methylation of TDRD1, appeared to be significantly associated with a higher risk for BCR (HR 3.96, 3.44, 2.80 and 2.85, correspondingly) after correcting for established risk factors. When DNA methylation was treated as a continuous variable, a two-gene model PITX2 × 0.020677 + HOXD3 × 0.0043132 proved to be the best predictor of BCR (HR 4.85) compared with the individual markers. This finding was confirmed in an independent set of 52 high-risk PCa tumor samples (HR 11.89). Conclusions: Differential promoter methylation of HOXD3, PITX2, RASSF1 and TDRD1 emerges as an independent predictor of BCR in high-risk PCa patients. A two-gene continuous DNA methylation model ' PITX2 × 0.020677 + HOXD3 × 0.0043132' is a better predictor of BCR compared with individual markers. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01715216
- Volume :
- 140
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Journal of Cancer Research & Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 98858094
- Full Text :
- https://doi.org/10.1007/s00432-014-1738-8