N-glycomic profiling of colorectal cancer according to tumor stage and location

Abstract

Alterations in glycosylation are seen in many types of cancer, including colorectal cancer (CRC). Glycans, the sugar moieties of glycoconjugates, are involved in many important functions relevant to cancer and can be of value as biomarkers. In this study, we have used mass spectrometry to analyze the N-glycan profiles of 35 CRC tissue samples and 10 healthy tissue samples from non-CRC patients who underwent operations for other reasons. The tumor samples were divided into groups depending on tumor location (right or left colon) and stage (II or III), while the healthy samples were divided into right or left colon. The levels of neutral and acidic N-glycan compositions and glycan classes were analyzed in a total of ten different groups. Surprisingly, there were no significant differences in glycan levels when all right-and left-sided CRC samples were compared, and few differences (such as in the abundance of the neutral N-glycan H3N5) were seen when the samples were divided according to both location and stage. Multiple significant differences were found in the levels of glycans and glycan classes when stage II and III samples were compared, and these glycans could be of value as candidates for new markers of cancer progression. In order to validate our findings, we analyzed healthy tissue samples from the right and left colon and found no significant differences in the levels of any of the glycans analyzed, confirming that our findings when comparing CRC samples from the right and left colon are not due to normal variations in the levels of glycans between the healthy right and left colon. Additionally, the levels of the acidic glycans H4N3F1P1, H5N4F1P1, and S1H5N4F1 were found to change in a cancer-specific but colon location-nonspecific manner, indicating that CRC affects glycan levels in similar ways regardless of tumor location.

Identification of Differential N-Glycan Compositions in the Serum and Tissue of Colon Cancer Patients by Mass Spectrometry

“…Bi-antennary mono-galactosylated and mono-galactosylated caped with one sialic acid compositions were overrepresented in tumor samples. Curiously, these forms are not usually found increased in CRC [ 19 ]. On the contrary, MS-based studies have shown a decrease rather than increase of bi-antennary compositions, mostly bisected forms [ 15 , 16 ].…”

“…Moreover, most of the current knowledge of the N-glycan profile in cancer has been based on quantification methods by LC-MS technology, such as adopted in this study, with characterization of N-glycan in a compositional level by accurate mass profiling [ 10 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 30 , 31 , 41 ]. Notwithstanding, we are aware that in-depth analysis of linkage positions and retention times of isomers or differential anomeric forms in LC/MS acquisitions, may add new insights on glycosylation as a source of biomarkers in cancer, what will surely deserve close attention in further studies.…”

“…Over the last 10 years, many studies have focused on the role of N-glycosylation in CRC. Albeit heterogeneous, colorectal tumors revealed a distinct pattern including increase of mannose rich, acidic N-glycans, core-fucosylated bi-antennary, multi-antennary sialylated and decrease of bisected forms in microenvironment of tumor samples [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

GeenaR: A Web Tool for Reproducible MALDI-TOF Analysis

“…We selected a study where researchers used mass spectrometry to analyze differences in N-glycan profiles between tumor and healthy samples. More details are reported in Holm et al (2020) .…”

The Role of Glycosyltransferases in Colorectal Cancer

“…As previously stated, alterations in glycosylation patterns, mediated by the modified glycosyltransferase expression, are involved in CRC malignant transformation [ 11 , 140 ]. Therefore, glycoconjugates and the molecules involved in their synthesis are interesting targets for new therapeutic approaches.…”