Comorbidity-Associated N-Glycome Profile Shifts: A Preliminary Study Evaluating COPD and Diabetes in Lung Cancer Patients

Aberrant glycosylation frequently accompanies malignant, metabolic, and chronic inflammatory diseases; however, it remains unclear how coexisting conditions influence disease-associated alterations in serum N-glycan profiles. To address this question, this preliminary study examined the influence of chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) on the N-glycan profiles in 40 patients with lung cancer (LC), divided into four groups (LC, LC + DM, LC + COPD, and LC + COPD + DM; n = 10 each). Released and fluorescently labelled N-glycans were profiled by capillary electrophoresis using laser-induced fluorescence detection. Peaks with a median relative peak area of ≥1% across the complete dataset were retained for quantitative analysis, resulting in a final set of 19 peaks. Peak-wise factorial models assessed DM, COPD, and their interaction while accounting for age and sex. When the peaks were analyzed individually, Peak 12, tentatively assigned to A3G(4)3S(6)2 by GU database matching (median GU 7.23), was the only peak that remained significant after multiple-testing correction. Descriptively, its mean relative peak area (%) was approximately 21% higher in DM-positive patients, while the adjusted model confirmed DM association on the logit scale. Likewise, analysis of the 19-peak serum N-glycan profile revealed a significant association with DM, whereas no significant effect of COPD or DM × COPD interaction was detected. F(6)A2B showed an exploratory DM-associated signal but did not remain significant after conventional multiple-testing correction. Our findings suggest that diabetes may be associated with a modest but detectable shift in the serum N-glycome profile of patients with lung cancer, with A3G(4)3S(6)2 representing the strongest structure-specific finding in this cohort. However, please note that under the more stringent joint correction across all 57 peak-effect tests, the HC3-based Peak 12 result did not reach the conventional significance threshold (FDR q = 0.055).