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Anterior gradient 2 (AGR2): Blood‐based biomarker elevated in metastatic prostate cancer associated with the neuroendocrine phenotype
Author(s) -
Kani Kian,
Malihi Paymaneh D.,
Jiang Yuqiu,
Wang Haiying,
Wang Yixin,
Ruderman Daniel L.,
Agus David B.,
Mallick Parag,
Gross Mitchell E.
Publication year - 2012
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22569
Subject(s) - prostate cancer , medicine , circulating tumor cell , pca3 , cancer , prostate , metastasis , biomarker , neuroendocrine differentiation , pathology , cancer research , oncology , biology , biochemistry
Abstract BACKGROUND Anterior gradient 2 (AGR2) is associated with metastatic progression in prostate cancer cells as well as other normal and malignant tissues. We investigated AGR2 expression in patients with metastatic prostate cancer. METHODS Blood was collected from 44 patients with metastatic prostate cancer separated as: castration sensitive prostate cancer (CSPC, n = 5); castration resistant prostate cancer (CRPC, n = 36); and neuroendocrine‐predominate CRPC defined by PSA ≤ 1 ng/ml in the presence of wide‐spread metastatic disease (NE‐CRPC, n = 3). AGR2 mRNA levels were measured with RT‐PCR in circulating tumor cell (CTC)‐enriched peripheral blood. Plasma AGR2 levels were determined via ELISA assay. AGR2 expression was modulated in prostate cancer cell lines using plasmid and viral vectors. RESULTS AGR2 mRNA levels are elevated in CTCs and strongly correlated with CTC enumeration. Plasma AGR2 levels are elevated in all sub‐groups. AGR2 levels vary independently to PSA and change in some patients in response to androgen‐directed and other therapies. Plasma AGR2 levels are highest in the NE‐CRPC sub‐group. A correlation between AGR2, chromagranin A (CGA), and neuron‐specific enolase (NSE) expression is demonstrated in prostate cancer cell lines. CONCLUSIONS We conclude that AGR2 expression is elevated at the mRNA and protein level in patients with metastatic prostate cancer. In particular, we find that AGR2 expression is associated features consistent with neuroendocrine, or anaplastic, prostate cancer, exemplified by an aggressive clinical phenotype without elevation in circulating PSA levels. Further studies are warranted to explore the mechanistic and prognostic implications of AGR2 expression in this patient population. Prostate 73: 306–315, 2013. © 2012 Wiley Periodicals, Inc.