title: Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy.
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.
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Corbin
authors.initials: C
authors.lastname: Jacobs
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Vasu
authors.initials: V
authors.lastname: Tumati
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Yan
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Xian-Jin
authors.initials: XJ
authors.lastname: Xie
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Raquibul
authors.initials: R
authors.lastname: Hannan
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Dong Wook Nathan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Saha
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D001706:Biopsy; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000532:radiotherapy; D011878:Radiotherapy; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C462952:DAB2IP protein, human; D020703:ras GTPase-Activating Proteins
keywords: Biomarker; DAB2IP; EZH2; prostate cancer; survival