High AGR2 protein is a feature of low grade endometrial cancer cells.

Kamal, Areege ORCID: 0000-0001-5239-9699, Valentijn, Anthony, Barraclough, Roger ORCID: 0000-0002-7203-1194, Rudland, Philip ORCID: 0000-0002-7491-0846, Rahmatalla, Nihad, Martin-Hirsch, Pierre, Stringfellow, Helen, Decruze, Shandya B and Hapangama, Dharani K ORCID: 0000-0003-0270-0150
(2018) High AGR2 protein is a feature of low grade endometrial cancer cells. Oncotarget, 9 (59). pp. 31459-31472.

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Background:Biomarkers for identification of endometrial cancers (ECs) with high risk of recurrence are required to reduce the rising EC-related mortality. AGR2 is a prognostic marker in several hormonally-regulated cancers. Aim:To assess the utility of AGR2 as a prognostic marker in EC. Methods:AGR2 immunoexpression was evaluated in 163 human endometrial samples. Change in AGR2 mRNA levels in response to oestrogen and dihydrotestosterone was studied in vitro. Results:Upregulation of AGR2 (protein and mRNA) was seen in low grade EC, compared to the postmenopausal endometrium (P = 0.013) and to the high-grade EC (P < 0.0001). Elevated AGR2 protein expression-scores were associated with a high expression of estrogen alpha (ERα), progesterone, androgen receptors and early clinical stages. Metastatic lesions maintained higher AGR2 expression relative to matched-primary tumors. High-AGR2 protein levels were associated with better overall survival (P = 0.02) in all ECs, but in highly-ERα-expressing ECs, AGR2 associated with unfavourable patient outcome. Androgen through its receptor, downregulated AGR2 mRNA in the Ishikawa cells. Conclusions:AGR2 is overexpressed in low grade ECs and positively associated with hormone receptors. The association between high AGR2 and progressive disease within the high-ERα-expressing ECs suggests that in this group of patients, AGR2 might be a potential biomarker of poor prognosis.

Item Type: Article
Uncontrolled Keywords: endometrial cancer, AGR2; metastasis, hormone regulation
Depositing User: Symplectic Admin
Date Deposited: 14 Sep 2018 09:13
Last Modified: 19 Jan 2023 01:25
DOI: 10.18632/oncotarget.25838
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3025862