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Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy
Journal article   Open access   Peer reviewed

Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy

Corbin Jacobs, Vasu Tumati, Payal Kapur, Jingsheng Yan, Xian-Jin Xie, Raquibul Hannan, Jer-Tsong Hsieh, Dong Wook Nathan Kim and Debabrata Saha
Cancer medicine (Malden, MA), Vol.4(12), pp.1844-1852
12/2015
DOI: 10.1002/cam4.554
PMCID: PMC4940806
PMID: 26471467
url
https://doi.org/10.1002/cam4.554View
Published (Version of record) Open Access

Abstract

Decreased expression of tumor suppressor DAB2IP is linked to aggressive cancer and radiation resistance in several malignancies, but clinical survival data is largely unknown. We hypothesized that pretreatment DAB2IP reduction would predict worse prostate cancer-specific survival (PCSS). Immunohistochemistry of pretreatment biopsies was scored by an expert genitourinary pathologist. Other endpoints analyzed include freedom from biochemical failure (FFBF), castration resistance-free survival (CRFS), and distant metastasis-free survival (DMFS). Seventy-nine patients with NCCN-defined high-risk prostate cancer treated with radiotherapy from 2005 to 2012 at our institution were evaluated. Twenty-eight percent (22/79) of pretreatment biopsies revealed DAB2IP-reduction. The median follow up times were 4.8 years and 5.3 years for patients in the DAB2IP-reduced group and DAB2IP-retained group, respectively. Patients with reduced DAB2IP demonstrated worse outcome compared to patients retaining DAB2IP, including FFBF (4-year: 34 vs. 92%; P < 0.0001), CRFS (4-year: 58 vs. 96%; P = 0.0039), DMFS (4-year: 58 vs. 100%; P = 0.0006), and PCSS (5-year: 83 vs. 100%; P = 0.0102). Univariate analysis showed T stage, N stage, and Gleason score were statistically significant variables. Pretreatment tumor DAB2IP status remained significant in multivariable analyses. This study suggests that about one-fourth of men with high-risk prostate cancer have decreased tumor expression of DAB2IP. This subpopulation with reduced DAB2IP has a suboptimal response and worse malignancy-specific survival following radiation therapy and androgen deprivation. DAB2IP loss may be a genetic explanation for the observed differences in aggressive tumor characteristics and radiation resistance. Further study into improving treatment response and survival in this subpopulation is warranted.
Radiotherapy Prostatic Neoplasms - metabolism Prostatic Neoplasms - radiotherapy ras GTPase-Activating Proteins - metabolism Follow-Up Studies Humans Middle Aged Kaplan-Meier Estimate Proportional Hazards Models Male Prostatic Neoplasms - diagnosis Biomarkers, Tumor Prostatic Neoplasms - mortality Neoplasm Grading Biopsy Aged Neoplasm Staging

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