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Immunoglobulin G N-Glycan Analysis by Ultra-Performance Liquid Chromatography
Published on: January 18, 2020
Exploring the potential causal role of IgG N-glycosylation in urological cancers: a two-sample Mendelian
1Department of Urology, Suzhou BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
Introduction:
Urological cancers pose a significant global health burden. Alterations in immunoglobulin G(IgG) N-glycosylation are implicated in cancer pathogenesis, but their causal role remains unclear. This study aimed to explore the potential causal associations between 77 specific IgG N-glycan traits (IGPs) and the risks of bladder, kidney, and prostate cancer.
Material And Methods:
We conducted a two-sample Mendelian randomization (MR) study using summary-level data. Genetic instruments for IGPs were obtained from a genome-wide association study (GWAS) of European descent. Outcome data were sourced from the FinnGen consortium. The inverse-variance weighted (IVW) method was the primary analysis, supplemented by multiple sensitivity analyses (MR-Egger, weighted median, MR-PRESSO, and MR-RAPS). The Steiger test was used to confirm causal direction.
Results:
After false discovery rate (FDR) correction, one association remained statistically significant. Using the IVW method, genetically predicted higher levels of IGP23 were significantly associated with a decreased risk of bladder cancer (OR = 0.78, p = 4.7e-04, FDR = 0.037). Thirteen additional nominal associations (p < 0.05) were observed for urological cancers (e.g., IGP10 for prostate cancer; IGP52, IGP73 for kidney cancer), although these did not withstand multiple testing correction. Sensitivity analyses showed no evidence of directional pleiotropy.
Conclusions:
Our study provides evidence supporting a potential causal association between the IgG N-glycan trait IGP23 and the risk of bladder cancer. Other nominal associations require further investigation. These findings highlight IGP23 as a candidate for future mechanistic and translational research in bladder cancer.