Smoking and lung cancer-induced changes in N-glycosylation of blood serum proteins

Abstract

Glycosylation is a key post-translational protein modification which appears important in malignant transformation and tumor metastasis. Abnormal glycosylation of different proteins can often be measured in the blood serum. In this study, we extend our serum-based structural investigations to samples provided by patients diagnosed with lung cancer, paying particular attention to the effects of smoking on the serum glycomic traces. Following a battery of glycomic tests, we find that several fucosylated tetra-antennary structures with varying degrees of sialylation are increased in their abundances in control samples provided by the former smokers, with further elevations in the lung cancer patients who were former smokers. Further detailed investigations demonstrated that the level of outer-arm fucosylation was elevated in the control samples of the former smokers and again in the lung cancer samples provided by the former smokers. This trend was particularly noticeable for the tri- and tetra-antennary structures. Different ratios of sialylation linkages were also observed that could be correlated with the different states of health and smoking status. Decreases in the abundance levels of isomers with two and three α2,3-linked sialic acids and an increased abundance of an isomer with two α2,6-linked sialic acids were noted for a fucosylated tri-sialylated tri-antennary glycan. These results demonstrate the long-term effects of smoking on glycomic profiles and that this factor needs to be considered in these and other serum-based analyses.

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

“…Smoking proved the only phenotype to positively associate with the fucosylation of tri-and tetraantennary species (A3F and A4F), as well as with the bisection of IgG-Fc type glycans (A2FS0B) (20,94). Likely these reflect the chronic response to vascular injury obtained from smoking-induced shear stress and oxidative damage (95).…”

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

“…Changes in fucosylation can be observed in nearly all malignancies, such as breast (16), hCC (17), colon (18) and lung cancer (19). high incidence of sLex in ER-negative breast tumors coincided with high expression of glycosyltransferases FUT3, FUT4 and ST3GAL6 (20).…”

New Trends in the Study of Protein Glycosylation in Oncological Diseases

“…Zatímco zánět, rakovina a imunologické procesy jsou propojeny v soubor komplexních mokutinách. Současný výzkum ukázal ně kte ré rozdíly na úrovni glykoproteinů -tvorbě glykanů v různých typech nádorů [11][12][13][14][15]. Nicméně není stále jasné, které proteiny nesou tyto modifi kace, protože ve výše uvedených studiích byly měřeny glykany, jež byly enzymaticky nebo chemicky odštěpeny z bio logických vzorků.…”

“…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.…”