Anterior Gradient-2 (AGR2) overexpression in colon cancer: a potential prognostic biomarker

Aims: Colon cancer is one of the most common leading causes of death worldwide. Prognostic at an early stage is an efficient way to decrease mortality. The Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a Protein Disulfide Isomerase (PDI) is highly expressed in various solid tumours and is involved in tumour microenvironment-associated processes such as tumour growth, invasion and metastasis. This study aims at examining the expression of AGR2 protein in colon cancer as its prognostic value in such cancer remains inconclusive. Methods: AGR2 protein expression was determined using immunohistochemistry on human tissue samples issued from a cohort of 82 colorectal carcinomas (Institut Bergonie, Bordeaux, France). Results: AGR2 protein expression was significantly higher in tumours than in adjacent non-tumour controls. AGR2 expression subgroup analyses indicated that AGR2 low expression in colon cancer patients was significantly associated with worse overall survival. Mucinous colon cancers exhibited higher AGR2 expression levels than non-mucinous cancers. Additionally, tumours with microsatellite instability (MSI) were characterised by a strong upregulation of AGR2 mRNA and protein expression despite an absence of MLH1/MSH2 mutations. Conclusion: Our findings indicate that high AGR2 protein expression is correlated with longer patient survival and that AGR2 overexpression is associated with MSI and mucinous-type colorectal cancers. Overall, AGR2 might serve as a biomarker to stratify colon tumours and to contribute to the prognosis of colon cancer patients.