Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in high-risk prostate cancer
Data(s) |
01/11/2014
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Resumo |
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. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/63509/1/Spahn_J%20Cancer%20Res_Methylation%20of%20PITX2.pdf Litovkin, Kirill; Joniau, Steven; Lerut, Evelyne; Laenen, Annouschka; Gevaert, Olivier; Spahn, Martin; Kneitz, Burkhard; Isebaert, Sofie; Haustermans, Karin; Beullens, Monique; Van Eynde, Aleyde; Bollen, Mathieu (2014). Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in high-risk prostate cancer. Journal of cancer research and clinical oncology, 140(11), pp. 1849-1861. Springer 10.1007/s00432-014-1738-8 <http://dx.doi.org/10.1007/s00432-014-1738-8> doi:10.7892/boris.63509 info:doi:10.1007/s00432-014-1738-8 info:pmid:24938434 urn:issn:1432-1335 |
Idioma(s) |
eng |
Publicador |
Springer |
Relação |
http://boris.unibe.ch/63509/ |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Litovkin, Kirill; Joniau, Steven; Lerut, Evelyne; Laenen, Annouschka; Gevaert, Olivier; Spahn, Martin; Kneitz, Burkhard; Isebaert, Sofie; Haustermans, Karin; Beullens, Monique; Van Eynde, Aleyde; Bollen, Mathieu (2014). Methylation of PITX2, HOXD3, RASSF1 and TDRD1 predicts biochemical recurrence in high-risk prostate cancer. Journal of cancer research and clinical oncology, 140(11), pp. 1849-1861. Springer 10.1007/s00432-014-1738-8 <http://dx.doi.org/10.1007/s00432-014-1738-8> |
Palavras-Chave | #610 Medicine & health |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |