Identification of Differential N-Glycan Compositions in the Serum and Tissue of Colon Cancer Patients by Mass Spectrometry
| Autor: | João Batista de Sousa, Marcelo de Melo Andrade Coura, Guilherme D. Brand, Carlos Bloch, Eder Alves Barbosa |
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| Přispěvatelé: | MARCELO DE M. A. COURA, UNB, EDER A. BARBOSA, UNB, GUILHERME D. BRAND, UNB, CARLOS BLOCH JUNIOR, Cenargen, JOAO B. DE SOUSA, UNB. |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Glycan QH301-705.5 Colorectal cancer colorectal cancer N-glycosylation Mass spectrometry Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine N-linked glycosylation Downregulation and upregulation Liquid chromatography–mass spectrometry medicine Biology (General) mass spectrometry Tumor microenvironment General Immunology and Microbiology biology Cancer LC/MS medicine.disease MALDI-TOF/MS carbohydrates (lipids) 030104 developmental biology 030220 oncology & carcinogenesis Cancer research biology.protein General Agricultural and Biological Sciences |
| Zdroj: | Biology Volume 10 Issue 4 Repositório Institucional da EMBRAPA (Repository Open Access to Scientific Information from EMBRAPA-Alice) Empresa Brasileira de Pesquisa Agropecuária (Embrapa) instacron:EMBRAPA Biology, Vol 10, Iss 343, p 343 (2021) |
| ISSN: | 2079-7737 |
| DOI: | 10.3390/biology10040343 |
| Popis: | Simple Summary Incidence of colorectal cancer (CRC) has been rising in Brazil. To date, no reliable biomarker has been described in CRC for diagnosis and prognosis. Modifications in the N-glycosylation profile are usually associated with many cancers, as CRC. In turn, mass spectrometry (MS)-based methods are the most accurate technology in quantification of N-glycans. Therefore, we described a unique pattern of compositions altered in serum and tissues of stages II and III colon cancer patients, identified by MALDI-TOF/MS and LC-MS technology. N-glycans were mostly found decreased in serum whilst oligomannosidic, hypogalactosylated, and tetra-antennary forms were overexpressed in tumor tissues. Total N-glycome in serum of cancer patients was different from the profile found in serum of healthy individuals. Strikingly, no correlation between tissue N-glycosylation profile and serum profile was observed in cancer patients, posing the question where these compositions are originated from. Abstract Colorectal cancer (CRC) ranks second as the leading cause of cancer-related deaths worldwide. N-glycosylation is one of the most common posttranslational protein modifications. Therefore, we studied the total serum N-glycome (TSNG) of 13 colon cancer patients compared to healthy controls using MALDI-TOF/MS and LC-MS. N-glycosylation of cancer tumor samples from the same cohort were further quantified using a similar methodology. In total, 23 N-glycan compositions were down-regulated in the serum of colon cancer patients, mostly galactosylated forms whilst the mannose-rich HexNAc2Hex7, the fucosylated bi-antennary glycan HexNAc4Hex5Fuc1NeuAc2, and the tetra-antennary HexNAc6Hex7NeuAc3 were up-regulated in serum. Hierarchical clustering analysis of TSNG correctly singled out 85% of the patients from controls. Albeit heterogenous, N-glycosylation of tumor samples showed overrepresented oligomannosidic, bi-antennary hypogalactosylated, and branched compositions related to normal colonic tissue, in both MALDI-TOF/MS and LC-MS analysis. Moreover, compositions found upregulated in tumor tissue were mostly uncorrelated to compositions in serum of cancer patients. Mass spectrometry-based N-glycan profiling in serum shows potential in the discrimination of patients from healthy controls. However, the compositions profile in serum showed no parallel with N-glycans in tumor microenvironment, which suggests a different origin of compositions found in serum of cancer patients. |
| Databáze: | OpenAIRE |
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