SWATH MS analysis of colorectal adenocarcinoma derived paired cellular model, namely SW480 derived from a primary tumour and SW620 derived from the tumour´s lymph node metastasis. The whole proteome spectra were analysed to assess the changes caused by the manipulation of AGR2 expression. AGR2, a protein disulphide isomerase, is often overexpressed in tumours and connected with proliferation, survival, chemoresistance, and metastasis. Parental SW480 is AGR2 negative, so a stable expressing clone was prepared, while SW620 is endogenously positive for AGR2; therefore, two CRISPR/Cas9 mediated knockout clones were generated. The SWATH MS analysis generated a set of differentially expressed proteins with respect to AGR2 expression. This allowed us to identify new potential regulatory mechanisms and molecular pathways in which the AGR2 might be involved.