Abstract
Simple SummaryIncidence 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.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.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide, with an annual incidence of approximately 1.8 million new cases, of which 900,000 are expected to die from this malignancy [1]
Two patients were excluded: a 57-year-old patient who refused to perform a genetic test for a germinative pathologic mutation and a 37-year-old patient with a well-differentiated adenocarcinoma in transverse colon, as he tested positive for germinative pathological mutation in MLH1 gene
Our study revealed a global decrease of galactosylated compositions present in serum of CRC patients by LC-mass spectrometry (MS) technology
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide, with an annual incidence of approximately 1.8 million new cases, of which 900,000 are expected to die from this malignancy [1]. Survival is closely related to clinical stage as fewer than 10% patients with metastatic disease will survive longer than 5 years. Patients with early diagnosis show a disease-free survival rate close to 90% [3]. Colonoscopy is the gold standard for diagnostic purposes in CRC, and albeit highly accurate, this is an invasive method, not exempt from complications. Many biomarkers currently in use, mostly carbohydrate antigens such as CEA and CA 19-9, show low sensitivity and specificity in CRC early detection [4]
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