Distribution of IgG galactosylation as a promising biomarker for cancer screening in multiple cancer types

Ren, Shifang; Zhang, Zejian; Xu, Congjian; Guo, Lin; Lu, Renquan; Sun, Yihong; Guo, Jianming; Qin, Ruihuan; Qin, Wenjun; Gu, Jianxin

doi:10.1038/cr.2016.83

Cited by 93 publications

(101 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, the panel with multiple IgG N-glycans may be of high performance in diagnostic models. The result of multiple cancer-type study indicated that the distribution of IgG galactosylation could be a promising biomarker for cancer screening, of which area under the curve of the Gal-ratio was 0.871 (95% CI: 0.879-0.903) (Ren et al, 2016). The distribution of IgG galactosylation (referred to as Gal-ratio) was measured by calculating the relative intensities of agalactosylated (G0) versus monogalactosylated (G1) and digalactosylated (G2) N-glycans according to the formula of G0/(G1 + G2 • 2).…”

Section: Discussion and Outlookmentioning

confidence: 99%

“…The body of evidence shows that the decrease in galactosylation is generally associated with reducing anti-inflammatory function of circulating IgG (Gudelj et al, 2018a;Liu et al, 2018b;Nikolac et al, 2014;Ren et al, 2016). In parallel, the reduction of sialic acid to the terminus of the Fc glycan can be inducing IgG antibody-driven inflammation (Anthony and Ravetch, 2010;Shade and Anthony, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Systematic Review: Immunoglobulin G N-Glycans as Next-Generation Diagnostic Biomarkers for Common Chronic Diseases

Liu

Zhang

et al. 2019

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

Glycomics is a new subspecialty in omics systems sciences that offers significant promise for next-generation biomarkers on disease susceptibility, drug target discovery, and precision medicine. In this context, alternative immunoglobulin G (IgG) N-glycosylation has been reportedly implicated in several common chronic diseases, although systematic assessment is currently lacking in the literature. We conducted a systematic review of observational studies on IgG N-glycan variability and susceptibility to common chronic diseases. Observational studies reporting an association between diseases (such as colorectal cancer, dyslipidemia, ischemic stroke, rheumatoid arthritis, and systemic lupus erythematosus) and IgG N-glycans quantified by ultraperformance liquid chromatography were included. The glycans were categorized into 24 initial IgG glycan peaks (GPs). Notably, aging positively correlated with GP1, GP2, GP4-7, GP10, GP11, GP19, and GP24, while negatively correlated with GP8, GP12-15, GP17, GP18, GP20, GP21, and GP23 (p < 0.05). The absolute value of significant correlation coefficients of age and IgG glycans ranged from 0.043 to 0.645. We found that the high levels of GP1-4, GP6, GP7, and GP24 and low levels of GP9, GP13-15, GP18, and GP23 could potentially increase the risk of disease. In conclusion, the present systematic review suggests that the field of glycomics, and GP1-4, GP6, GP7, GP9, GP13-15, GP18, GP23, and GP24 in particular, holds promise for further candidate biomarker research on susceptibility to common chronic diseases.

show abstract

Section: Discussion and Outlookmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systematic Review: Immunoglobulin G N-Glycans as Next-Generation Diagnostic Biomarkers for Common Chronic Diseases

Liu

Zhang

et al. 2019

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

show abstract

“…Immunoglobin G (IgG), the most abundant glycoprotein in blood, is closely correlated with immune status. Recent studies have indicated the importance of altered glycosylation patterns of IgG in autoimmune diseases, infectious diseases, and different types of cancer [18][19][20]. Although several studies have reported declining levels of galactosylated N-glycans and bisecting GlcNAc structures on IgG in lung cancer [21][22][23], no studies have investigated the relationship between IgG glycosylation and pathological staging of small-sized pulmonary nodules.…”

Section: Introductionmentioning

confidence: 99%

Glycomic Signatures of Plasma IgG Improve Preoperative Prediction of the Invasiveness of Small Lung Nodules

et al. 2019

View full text Add to dashboard Cite

Preoperative assessment of tumor invasiveness is essential to avoid overtreatment for patients with small-sized ground-glass nodules (GGNs) of 10 mm or less in diameter. However, it is difficult to determine the pathological state by computed tomography (CT) examination alone. Aberrant glycans has emerged as a tool to identify novel potential disease biomarkers. In this study, we used a lectin microarray-based strategy to investigate whether glycosylation changes in plasma immunoglobulin G (IgG) provide additional information about the invasiveness of small GGNs before surgery. Two independent cohorts (discovery set, n = 92; test set, n = 210) of GGN patients were used. Five of 45 lectins (Sambucus nigra agglutinin, SNA; Datura stramonium agglutinin, DSA; Galanthus nivalis agglutinin, GNA; Euonymus europaeus lectin, EEL; and Vicia villosa agglutinin, VVA) were identified as independent factors associated with pathological invasiveness of small GGNs (p < 0.01). Receiver-operating characteristic (ROC) curve analysis indicated the combination of these five lectins could significantly improve the accuracy of CT in diagnosing invasive GGNs, with an area under the curve (AUC) of 0.792 (p < 0.001), a sensitivity of 74.6%, and specificity of 74.4%, which was superior to current clinical biomarkers. These results suggest that the multilectin assay based on plasma IgG glycosylation may be a useful in vitro complementary test to enhance preoperative determination of the invasiveness of GGNs and guide surgeons to select proper clinical management to avoid overtreatment.

show abstract

“…Early studies showed that β-1,4-galactosylation on IgG glycans is lowered in individuals with rheumatoid arthritis (RA) or primary osteoarthritis (1,2). Since then, other (chronic) inflammatory diseases have been shown to be associated with IgG undergalactosylation, including several cancers (3,4), inflammatory bowel disease (5,6), systemic lupus erythematosus (7) and liver disease (8)(9)(10). Remarkably, in RA and hepatitis B virus (HBV) patients, the glycosylation patterns normalize after treatment (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Endoglycosidase S enables a highly simplified clinical chemistry assay procedure for direct assessment of serum IgG undergalactosylation in chronic inflammatory disease

Vanderschaeghe

Meuris

Raes

et al. 2018

Preprint

View full text Add to dashboard Cite

Over the past 30 years, it has been firmly established that a wide spectrum of (autoimmune) diseases such as rheumatoid arthritis, Crohn’s and lupus, but also other pathologies like alcoholic and non-alcoholic steatohepatitis (ASH and NASH) are driven by chronic inflammation and are hallmarked by a reduced level of serum IgG galactosylation. IgG (under)galactosylation is a promising biomarker to assess disease severity, and monitor and adjust therapy. However, this biomarker has not been implemented in routine clinical chemistry due to a complex analytical procedure that necessitates IgG purification, which is difficult to perform and validate at high throughput.We addressed this issue by using endo-β-N-acetylglucosaminidase from Streptococcus pyogenes (endoS) to specifically release Fc N-glycans in whole serum. The entire assay can be completed in a few hours and only entails adding endoS and labeling the glycans with APTS. Glycans are then readily analyzed through capillary electrophoresis. We demonstrate in two independent patient cohorts that IgG undergalactosylation levels obtained with this assay correlate very well with scores calculated from PNGaseF-released glycans of purified antibodies. Our new assay allows to directly and specifically measure the degree of IgG galactosylation in serum through a fast and completely liquid phase protocol, without the requirement for antibody purification. This should help advancing this biomarker towards clinical implementation.

show abstract

Distribution of IgG galactosylation as a promising biomarker for cancer screening in multiple cancer types

Cited by 93 publications

References 9 publications

Systematic Review: Immunoglobulin G N-Glycans as Next-Generation Diagnostic Biomarkers for Common Chronic Diseases

Systematic Review: Immunoglobulin G N-Glycans as Next-Generation Diagnostic Biomarkers for Common Chronic Diseases

Glycomic Signatures of Plasma IgG Improve Preoperative Prediction of the Invasiveness of Small Lung Nodules

Endoglycosidase S enables a highly simplified clinical chemistry assay procedure for direct assessment of serum IgG undergalactosylation in chronic inflammatory disease

Contact Info

Product

Resources

About