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

The cover for issue 59 of Oncotarget features Figure 4, "The expression of AGR2 in metastatic lesions," by Kamal, et al.

Elevated AGR2 protein expression-scores were associated with a high expression of estrogen alpha, progesterone, androgen receptors and early clinical stages. High-AGR2 protein levels were associated with better overall survival in all ECs, but in highly-ER -expressing ECs, AGR2 associated with unfavorable patient outcome. The association between high AGR2 and progressive disease within the high-ER -expressing ECs suggests that in this group of patients, AGR2 might be a potential biomarker of poor prognosis.

Dr. Dharani K. Hapangama from the Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK and the Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK said, "Endometrial cancer is the most common gynecological cancer in the Western world and the incidence is expected to double by 2025; EC-associated mortality also is increasing in an era of decreasing cancer-related mortality in many other cancers."

Figure 4: The expression of AGR2 in metastatic lesions. (A) photomicrographs showing the immunoexpression of AGR2 in HGEC primary endometrial cancer and matched metastatic lesion (×400 magnification). (B) Immunoscores of AGR2 in primary tumours vs matched metastases.

AGR2 is the human homologue of Xenopus laevis Anterior Gradient, a protein that belongs to the protein disulfide isomerase family of endoplasmic reticulum-resident proteins. AGR2 can also be secreted and is detected in extracellular fluids; hence AGR2 protein has been proposed as a compelling biomarker for cancer detection and/or follow-up.

In this study, changes in the levels of endometrial AGR2 protein/AGR2 mRNA expression are shown for the first time across the normal pre and postmenopausal endometrium, premalignant atypical endometrial hyperplasia, EC and in matched metastatic lesions. The prognostic significance of AGR2 expression is also assessed in the research team's cohort and further validated using The Cancer Genome Atlas EC series.

The Dharani K. Hapangama research team concluded, "We observed that the high AGR2 quick scores significantly correlated with positive protein expression scores for ER, PR and AR, suggesting a possible role for E2 in AGR2 regulation. However, this is in contrast to a recent study showing that both estrogen and tamoxifen induced AGR2 protein expression in Ishikawa cells after 24 hours. Although the AR antagonist did not completely restore the basal level of AGR2 mRNA, we can conclude that down regulation of the AGR2 gene can be, at least partially induced through AR."

Full text - https://doi.org/10.18632/oncotarget.25838

Correspondence to - Dharani K. Hapangama - dharani@liv.ac.uk

Keywords - endometrial cancer, AGR2, metastasis, hormone regulation