Serum Proteomics on the Basis of Discovery of Predictive Biomarkers of Response to Androgen Deprivation Therapy in Advanced Prostate Cancer

Manish Kohli, Ann L Oberg, Douglas W. Mahoney, Shaun M. Riska, Robert Sherwood, Yuzi Zhang, Roman M. Zenka, Deepak Sahasrabudhe, Rui Qin, Sheng Zhang

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Abstract

Background: We investigated the serum proteome of hormone-sensitive prostate cancer patients to determine candidate biomarkers associated with androgen deprivation therapy (ADT)efficacy. Patients and Methods: Serum proteomes generated using isobaric mass tags for relative and absolute quantitation were analyzed using reverse-phase liquid chromatography coupled to tandem mass spectrometry. The advanced hormone-sensitive prostate cancer cohorts studied were: (1)untreated “paired” pre-ADT and 4-month post-ADT hormone-sensitive patients (n = 15); (2)“early ADT failure” patients (n = 10)in whom ADT treatment failed within a short period of time; and (3)“late ADT failure” patients (n = 10)in whom ADT treatment failed after a prolonged response time. Differential abundance was assessed, and ingenuity pathway analysis (IPA)was used to identify interaction networks in selected candidates from these comparisons. Results: Between “post-ADT” and combined “early” and “late” ADT failure groups 149 differentially detected candidates were observed, and between “early” and “late” ADT failure groups 98 candidates were observed; 47 candidates were common in both comparisons. IPA network enrichment analysis of the 47 candidates identified 3 interaction networks (P <.01)including 17-β-estradiol, nuclear factor kappa-light-chain enhancer of activated B cells complex, and P38 mitogen-activated protein kinases as pathways with potential markers of response to ADT. Conclusion: A global proteomic analysis identified pathways with markers of ADT response, which will need validation in independent data sets.

Original languageEnglish (US)
JournalClinical Genitourinary Cancer
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Hormonal therapy
  • Predictive factors
  • Prostate cancer
  • Proteomics
  • Serum

ASJC Scopus subject areas

  • Oncology
  • Urology

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