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Abstract

Volume 12, Issue 2 (March 2010) 12, 171–179; 10.1038/aja.2009.81

Application of histone modification in the risk prediction of the biochemical recurrence after radical prostatectomy

Li-Xin Zhou*, Tao Li*, Yi-Ran Huang, Jian-Jun Sha, Peng Sun, Dong Li

Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China

* These two authors contribute equally to this work.

Correspondence: Dr Dong Li, lidong.rj009@yahoo.com.cn

Received: 21 June 2009 Revised: 30 July 2009 Accepted: 4 November 2009 Published online: 23 November 2009

Abstract

The role of histone modifications in the development and progression of cancer remains unclear. Here, we gave an investigation of the relationship between the various histone modifications and the risk prediction of the biochemical recurrence after radical prostatectomy (RP). Histone 3 lysine 4 dimethylation (H3K4diMe), trimethylation (H3K4triMe), lysine 36 trimethylation (H3K36triMe), histone 4 lysine 20 trimethylation (H4K20triMe) and acetylation of histome 3 lysine 9 (H3K9Ac) were evaluated using immnuohistochemistry coupled with the tissue microarray technique in 169 primary prostatectomy tissue samples. Recursive partitioning analysis (RPA) was used to analyze the data. Through global histone modification analysis in patients who underwent radical prostatectomy, we found that H3K4triMe can predict the risk of the biochemical recurrence for the low grade prostate cancer (Gleason score ≤ 6) after RP. In the case of high grade prostate cancer (Gleason score ≥ 7), H4K20triMe and H3K9Ac accompanying with the pre-operation prostate-specific antigen (PSA) level could also predict the risk of the biochemical recurrence after RP. In combination with the Gleason score and pre-operation PSA level, the acetylation and methylation of histones H3 and H4 can predict the biochemical recurrence of the prostate cancer following RP.

Keywords: biochemical recurrence; histone modification; immunohistochemistry; prostate cancer; radical prostatectomy; tissue microarray

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