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

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.

journal_name

Clin Genitourin Cancer

journal_title

Clinical genitourinary cancer

authors

Kohli M,Oberg AL,Mahoney DW,Riska SM,Sherwood R,Zhang Y,Zenka RM,Sahasrabudhe D,Qin R,Zhang S

doi

10.1016/j.clgc.2019.03.006

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

248-253.e7

issue

4

eissn

1558-7673

issn

1938-0682

pii

S1558-7673(18)30661-X

journal_volume

17

pub_type

杂志文章

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