Journal article
DOC-2/DAB2 interacting protein status in high-risk prostate cancer correlates with outcome for patients treated with radiation therapy
International journal of radiation oncology, biology, physics, Vol.89(4), pp.729-735
07/15/2014
DOI: 10.1016/j.ijrobp.2014.03.035
PMCID: PMC4464555
PMID: 24867541
Abstract
This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy. Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance-free survival (CRFS), and distant metastasis-free survival (DMFS). Log-rank test and Cox regression were used to determine significance of biomarker levels with clinical outcome. Fifty-four patients with high-risk prostate cancer (stage ≥ T3a, or Gleason score ≥ 8, or prostate-specific antigen level ≥ 20 ng/mL) treated with radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2 study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%, P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%, P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04) compared with the control group. Loss of DAB2IP is a potent biomarker that portends worse outcome despite definitive radiation therapy for patients with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most high-risk tumors and is a less potent discriminator of outcome in this study. The DAB2IP status in combination with degree of EZH2 expression may be useful for determining patients with worse outcome within the high-risk prostate cancer population.
Details
- Title: Subtitle
- DOC-2/DAB2 interacting protein status in high-risk prostate cancer correlates with outcome for patients treated with radiation therapy
- Creators
- Corbin Jacobs - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TexasVasu Tumati - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TexasPayal Kapur - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TexasJingsheng Yan - Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TexasDavid Hong - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TexasManzerul Bhuiyan - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TexasXian-Jin Xie - Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TexasDavid Pistenmaa - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Simmons Cancer Center, Dallas, TexasLan Yu - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TexasJer-Tsong Hsieh - Simmons Cancer Center, Dallas, Texas; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TexasDebabrata Saha - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Simmons Cancer Center, Dallas, TexasD W Nathan Kim - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Simmons Cancer Center, Dallas, Texas. Electronic address: Nathan.Kim@utsouthwestern.edu
- Resource Type
- Journal article
- Publication Details
- International journal of radiation oncology, biology, physics, Vol.89(4), pp.729-735
- Publisher
- United States
- DOI
- 10.1016/j.ijrobp.2014.03.035
- PMID
- 24867541
- PMCID
- PMC4464555
- ISSN
- 1879-355X
- eISSN
- 1879-355X
- Grant note
- R21 CA175879 / NCI NIH HHS
- Language
- English
- Date published
- 07/15/2014
- Academic Unit
- Preventive and Community Dentistry; Biostatistics; Dental Research
- Record Identifier
- 9983917782502771
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