Clinical utility of a serum glycome analysis in patients with colorectal cancer

Abstract

Background and Aim: Serum glycans are known to be good markers for the early diagnosis and prognostic prediction in many cancers. The aims of this study were to reveal the serum glycan changes comprehensively during the process of carcinogenesis from colorectal adenoma (CRA) to colorectal cancer (CRC) and to evaluate the usefulness of the glycan profiles as clinical markers for CRC. Methods: Serum samples were obtained from 80 histologically proven CRC and 36 CRA cases. The levels of glycans in the serum were examined with a comprehensive, quantitative, high-throughput unique glycome analysis, and their diagnostic and prognostic abilities were evaluated. Results: Among 34 stably detected glycans, nine were differentially expressed between CRC and CRA. Serum levels of hybrid type glycans were increased in patients with CRC compared with those with CRA (P < 0.001), and both hybrid-type and multi-antennary glycans were significantly increased in advanced cancer cases. The glycan, m/z 1914, showed the highest diagnostic value among the decreased glycans, whereas m/z 1708 showed the highest among the increased glycans. The glycan ratio m/z 1708/1914 showed a higher area under the receiver operating characteristic curve (0.889) than any other single glycan or conventional tumor marker, such as carcinoembryonic antigen (0.766, P = 0.040) and carbohydrate antigen 19-9 (0.615, P < 0.001). High m/z 1708/1914 was also correlated with an advanced cancer stage and short overall survival. Conclusion: Serum glycans, especially the m/z 1708/1914 ratio, were useful for the diagnosis, staging, and prognosis prediction of CRC.

Serum N-Glycosylation RPLC-FD-MS Assay to Assess Colorectal Cancer Surgical Interventions

“…The alteration of these eight significant N -glycans in CRC is displayed in Figure 2 , which shows a lower pre-operative expression of H4N4F1, H5N4F1, H5N4F1S 2,6 1, and H5N4F1S 2,3 2. These results are in line with previous reports that di-antennary structures with core fucosylation are decreased in CRC [ 14 , 25 , 26 , 27 ]. In addition, we also observed that H5N5F1 has a lower abundance in pre-operative CRC, which is supported by previous findings whereby bisected N -glycan species were also found to be decreased in serum as well as tissues from CRC patients [ 14 , 25 , 28 ].…”

“…In relation to this, the isotopic profile of H6N5S 2,3 1S 2,6 2 (isomer 2) is shown in Supplementary Figure S1 . Takei et al analyzed the serum N -glycome using a previous iteration of the Bruker MALDI instrument, the ultraflex III, which resulted in the quantification of 34 N -glycans [ 25 ]. Thus, it is likely that the current workflow could be improved by coupling with a mass spectrometer with higher resolving power and greater sensitivity.…”

Polysaccharide of Lactobacillus casei SB27 reduced colon cancer cell prognosis through mitochondrial damage by upregulation of HINT2

“…CRC is one of the most common malignant tumors of digestive system in clinical practice and ranks third in the incidence rate of cancer worldwide 12 . Over the past 30 years, the living standards of the people have been improving, and the diet structure has changed 13 .…”

“…CRC is one of the most common malignant tumors of digestive system in clinical practice and ranks third in the incidence rate of cancer worldwide. 12 Over the past 30 years, the living standards of the people have been improving, and the diet structure has changed. 13 Most countries including China have experienced an increasing incidence rate of CRC, which has seriously endangered people's health.…”

Warning signs from the crypt: Aberrant protein glycosylation marks opportunities for early colorectal cancer detection.

“…This was recently addressed in a study using ultra performance liquid chromatography and demonstrating distinct serum IgG N-glycan profiles for AA and CRC ( 92 ). Another group studying 34 serum glycans reported that 9 of both hybrid-type and multiantennary glycans were differentially expressed between CRC and AA ( 93 ). Not only glycosylated proteins but also glycan-binding proteins such as galectin-2, galectin-3, galectin-4, and galectin-8 are found to be elevated in the serum from patients with CRC.…”