Glycomic alterations in the highly-abundant and lesser-abundant blood serum protein fractions for patients diagnosed with hepatocellular carcinoma

Abstract

Hepatocellular cancer is a serious human disease with an unfortunately low survival rate. It further poses a significant epidemic threat to our society through its viral vectors associated with cirrhosis conditions preceding the cancer. A search for biomarkers of these diseases enlists analytical glycobiology, in general, and quantitative biomolecular mass spectrometry (MS), in particular, as valuable approaches to cancer research. The recent advances in quantitative glycan permethylation prior to MALDI-MS oligosaccharide profiling has enabled us to compare the glycan quantitative proportions in the small serum samples of cancer and cirrhotic patients against control individuals. We were further able to fractionate the major serum proteins from the minor components and compare statistically their differential glycosylation, elucidating some causes of quantitatively unusual glycosylation events. Numerous glycan structures were tentatively identified and connected with the origin proteins, with a particular emphasis on sialylated and fucosylated glycans.

Human Plasma N-glycosylation as Analyzed by Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance-MS Associates with Markers of Inflammation and Metabolic Health

“…Although similarly sized investigations have analyzed plasma N-glycosylation by separation techniques like (U) HPLC or CGE-LIF (18 -20, 23, 70), to our knowledge this is the largest study of its kind performed by MS (32)(33)(34). Glycan compositions as obtained by MS provide orthogonal information to chromatographic peaks.…”

“…Mass spectrometry provides orthogonal information from these methodologies, as it does not distinguish isomers but instead unambiguously evaluates glycans on a compositional level (29 -31). To date, a large mass spectrometric TPNG study remains to be performed for revealing associations with markers of inflammation and metabolic health (32)(33)(34).…”

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

“…Hence, some glycoproteins have been suggested as biomarkers of human carcinomas such as ovarian cancer, breast cancer, and HCC. [16][17][18][19] Of note, changes to the N-linked glycan modification of glycoproteins occur during the tumorigenesis and progression of HCC lesions. However, the correlation between the N-glycan profile and tumorassociated characteristics such as the degree of malignancy and prognosis has not been previously evaluated in HCC.…”

New Trends in the Study of Protein Glycosylation in Oncological Diseases

“…Ukázalo se rovněž být slibným přístu-pem při určení stadia nádorového onemocnění mléčné žlázy [32] a zvýraz-nilo další glykanové profi ly u rakoviny jícnu [33], jater [12,34], vaječníků [13], plic [14] a tlustého střeva [15]. Příklady glykanového profi lování vzorků sér pocházejících od pacientek s nádorem vaječníků založeného na MALDI/ MS jsou znázorněny na obr.…”