Anterior gradient 2 (AGR2): Blood‐based biomarker elevated in metastatic prostate cancer associated with the neuroendocrine phenotype

Abstract

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.

Anterior gradient 2: A novel sensitive tumor marker for metastatic oral cancer

“…AGR2 belongs to the protein disulfide isomerase (PDI) family that is involved in the regulation of cell-cell interaction and actin filament polymerization [32]. It is also an independent prognostic factor in high-grade ovarian carcinoma and a biomarker for metastatic prostate cancer [33,34]. Although the overexpression of the AGR2 gene and protein has been reported to be associated with several adenocarcinoma cancers including colon, lung, breast, gastrointestinal, and pancreatic cancers [14,15,17], very few investigations have demonstrated the overexpression of AGR2 in squamous cell carcinomas [31].…”

“…Up-regulation of AGR2 expression was reported in both hormone-dependent cancers (breast, ovarian and prostate) and hormone-independent cancers (lung, liver, colorectal, esophageal, gastric and others cancers) [14,15]. Pohler et al demonstrated that AGR2 acts as a p53 inhibitor and subsequently promotes cancer metastasis [16].…”

Regulation of tumor cell plasticity by the androgen receptor in prostate cancer

“…Indeed, prolonged exposure to IL6 can reduce AR expression (Debes et al 2005), which further suggests that there is an important link between this cytokine and an AR-negative NEPC phenotype. In addition, a number of genes are up-regulated after ADT, and they are thus presumed to be androgen-suppressed and are associated with a progression to NEPC or non-AR-driven 'anaplastic' CRPC, including ARG2 (Kani et al 2013), hASH-1 (Rapa et al 2013) and protocadherins (Terry et al 2013). Importantly however, although many studies have shown an inverse correlation between NEPC and AR expression or activity, no reports have indicated a direct mechanism by which a loss of AR actually drives this phenotype.…”

Expression of AGR2 in pituitary adenomas and its association with tumor aggressiveness

“…AGR2 has been reported to be overexpressed in several adenocarcinomas, including breast (5), colorectal (6), ������g��l (7), l��g (8), ���c�����c (9) ��� �������� (10,11) carcinomas. ARG2 is considered to promote cell proliferation, cell survival and the metastasis of cancer cells.…”