The Plasma Glycome Differences Between Women with PCOS and Healthy Controls

While PCOS research has extensively explored genomic, transcriptomic, proteomic, and metabolomic milieus, our study examines the plasma glycome, comparing women with PCOS to age-matched healthy controls. In this observational study, n = 47 women with PCOS were screened and enrolled at the UC Davis Health campus; the comparator group constituted of n = 25 age-matched healthy women. During a study visit, body weight and body composition were measured, and fasted plasma samples were obtained to measure glucose, insulin, circulating lipids, and leptin, among other parameters, in both groups. In addition, in the PCOS group, circulating androgens and other endocrine hormones were measured. The plasma glycome was measured using a UHPLC-MS protocol. As expected, women with PCOS had higher body weight (<i>p</i> < 0.01), body fat (<i>p</i> = 0.004), fasting leptin (<i>p</i> = 0.01), insulin (<i>p</i> = 0.003), and glucose (<i>p</i> = 0.004). Hybrid-type glycans were reduced (<i>p</i> = 0.019), while tetraantennary (glycans with four branches) were modestly increased (<i>p</i> = 0.05) in women with PCOS compared to healthy controls. SVEM-LASSO (bootstrapped) regression models further supported a higher tetraantennary and lower hybrid glycan profile as representative of women with PCOS (AUROC: 0.81, accuracy: 82), even when adjusted for body weight (AUROC: 0.89, accuracy: 80) and body fat mass (AUROC: 0.89, accuracy: 86). Furthermore, in women with PCOS, total testosterone was positively correlated with tetraantennary glycans (r = 0.322, <i>p</i> = 0.029). We report novel findings of elevated tetraantennary and reduced hybrid-type N-glycans in PCOS, and a potential association between circulating androgens and protein glycosylation. Given the pilot nature of this study, larger cohort investigations are required to validate these observations.