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, Debabrata Saha

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1844-1852
Number of pages9
JournalCancer Medicine
Volume4
Issue number12
DOIs
StatePublished - 2015

Fingerprint

Prostatic Neoplasms
Radiotherapy
Biopsy
Survival
Neoplasms
Castration
Radiation
Neoplasm Metastasis
Neoplasm Grading
Androgens
Immunohistochemistry

Keywords

  • Biomarker
  • DAB2IP
  • EZH2
  • prostate cancer
  • survival

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy. / Jacobs, Corbin; Tumati, Vasu; Kapur, Payal; Yan, Jingsheng; Xie, Xian Jin; Hannan, Raquibul; Hsieh, Jer Tsong; Kim, Dong Wook Nathan; Saha, Debabrata.

In: Cancer Medicine, Vol. 4, No. 12, 2015, p. 1844-1852.

Research output: Contribution to journalArticle

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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.",
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AU - Xie, Xian Jin

AU - Hannan, Raquibul

AU - Hsieh, Jer Tsong

AU - Kim, Dong Wook Nathan

AU - Saha, Debabrata

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