Anterior Gradient-2 (AGR2) is overexpressed in colon cancer and is a potential biomarker of microsatellite instability (MSI) tumors

Background 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 tumours and is involved in tumour-associated processes. This study aims at examining the expression of AGR2 protein in colon cancer. Methods AGR2 protein expression was determined using immunohistochemistry on tissue samples issued from a cohort of 82 colorectal carcinomas. Results AGR2 protein expression was significantly higher in tumours than in adjacent nontumour 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. Conclusions Our findings indicate that high AGR2 protein expression is correlated with longer patient survival and that AGR2 overexpression is associated with MSI tumours and could represent an MSI biomarker. Overall, AGR2 might serve as a biomarker to stratify colon tumours and to contribute to the prognosis of colon cancer patients. ### Competing Interest Statement The authors have declared no competing interest. * ANT : Adjacent Non-Tumour tissues AGR2 : Anterior Gradient-2 CIN : Chromosome Instable cAGR2 : cytosolic AGR2 ER : Endoplasmic Reticulum EMT : Epithelial-to-Mesenchymal Transition eAGR2 : extracellular AGR2 GS : Genome Stable IHC : Immunohistochemical MSI : Microsatellite Instability MMR : Mismatch Repair MUC2 : Mucin 2 pN-status : Nodal status POLE : Polymerase e mutated PDI : Protein Disulfide Isomerase TCGA : The Cancer Genome Atlas pT-status : Tumour status T : Tumour tissues UPR : Unfolded Protein Response