N-Glycomic Signature of Stage II Colorectal Cancer and Its Association With the Tumor Microenvironment

The choice for adjuvant chemotherapy in stage II colorectal cancer is controversial as many patients are cured by surgery alone and it is difficult to identify patients with high risk of recurrence of the disease. There is a need for better stratification of this group of patients. Mass spectrometry imaging could identify patients at risk. We report here the N-glycosylation signatures of the different cell populations in a group of stage II colorectal cancer tissue samples. The cancer cells, compared with normal epithelial cells, have increased levels of sialylation and high-mannose glycans, as well as decreased levels of fucosylation and highly branched N-glycans. When looking at the interface between cancer and its microenvironment, it seems that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome within this sample group.
Graphical Abstract
Highlights • N-glycan MS imaging as tool for better cancer stratification. • Increased levels of sialylated and high-mannose glycans in CRC stage II cancer. • Characterization of the interaction between cancer and its direct microenvironment. • Insight into N-glycosylation signature of high-risk patients with short survival.
In Brief There is a need for better stratification of patients with stage II colorectal cancer as the treatment option remains controversial. Using MS imaging, we have characterized the N-glycosylation signatures of the different cell populations in stage II CRC tissues. We found, looking at the tumor microenvironment, that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome.