Ukkola, I.; Nummela, P.; Heiskanen, A.; Holm, M.; Zafar, S.; Kero, M.; Haglund, C.; Satomaa, T.; Kytölä, S.; Ristimäki, A. N-Glycomic Profiling of Microsatellite Unstable Colorectal Cancer. Cancers2023, 15, 3571.
Ukkola, I.; Nummela, P.; Heiskanen, A.; Holm, M.; Zafar, S.; Kero, M.; Haglund, C.; Satomaa, T.; Kytölä, S.; Ristimäki, A. N-Glycomic Profiling of Microsatellite Unstable Colorectal Cancer. Cancers 2023, 15, 3571.
Ukkola, I.; Nummela, P.; Heiskanen, A.; Holm, M.; Zafar, S.; Kero, M.; Haglund, C.; Satomaa, T.; Kytölä, S.; Ristimäki, A. N-Glycomic Profiling of Microsatellite Unstable Colorectal Cancer. Cancers2023, 15, 3571.
Ukkola, I.; Nummela, P.; Heiskanen, A.; Holm, M.; Zafar, S.; Kero, M.; Haglund, C.; Satomaa, T.; Kytölä, S.; Ristimäki, A. N-Glycomic Profiling of Microsatellite Unstable Colorectal Cancer. Cancers 2023, 15, 3571.
Abstract
Aberrant glycosylation affects cancer progression and immune evasion. Approximately 15% of colorectal cancers (CRCs) demonstrate microsatellite instability (MSI) and display major differences in outcomes and therapeutic responses as compared to corresponding microsatellite stable (MSS) tumors. We compared the N-glycan profiles of stage II and IV MSI CRC tumors, further subdivided into BRAFV600E wild-type and mutated subgroups (n=10 in each subgroup), with each other and with those of paired non-neoplastic mucosal samples using mass spectrometry. Further, the N-glycans of BRAFV600E wild-type stage II MSI tumors were compared to corresponding MSS tumors (n=9). Multiple differences in N-glycan profiles were identified between MSI CRCs and control tissues, as well as between stage II MSI and MSS samples. MSI CRC tumors showed a lower relative abundance of high-mannose N-glycans than the control tissues or the MSS CRCs. Among MSI CRC subgroups, acidic N-glycans showed tumor stage and BRAF mutation status dependent variation. Especially large, sulfated/phosphorylated, and putative terminal N-acetylhexosamine containing acidic N-glycans differed between the MSI CRC subgroups, showing opposite changes in stage II and IV, when comparing BRAF mutated and wild-type tumors. Our results show that molecular subgroups of CRC have characteristic glycan profiles that may explain certain carcinogenic properties of MSI tumors.
Keywords
BRAFV600E; colorectal cancer; microsatellite instability; mass spectrometry; N-glycosylation
Subject
Medicine and Pharmacology, Pathology and Pathobiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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