IgG Gal-ratio, a promising serum biomarker for detecting ovarian cancer in as early as stage I disease

Early detection of epithelial ovarian cancer (EOC) is hampered by the absence of an ideal serum biomarker. This study aimed to further validate the utility of IgG Gal-ratio in pre-operative diagnosis of ovarian cancer. Serum samples were collected from patients presenting with pelvic mass or elevated serum CA125 levels before surgery at the Obstetrics & Gynecology Hospital of Fudan University between June 2017 and December 2019. IgG was purified from these samples and incubated with PNGase F to release IgG N-glycans. Oligosaccharides from each sample were analyzed and quantified using MALDI-QIT-TOF MS and tandem MS. The IgG Gal-ratio was calculated as G0/ (G1 + G2 × 2), where G0, G1, and G2 represent the intensities of biantennary, core-fucosylated structures with zero, one, and two galactose residues, respectively. The levels of IgG Gal-ratio were compared among patients with EOC, ovarian borderline tumors (BOT), and benign gynecological conditions using Student’s t-test. Receiver operating characteristic curve were plotted, and sensitivity and specificity were calculated to assess the diagnostic power of IgG Gal-ratio for ovarian cancer. A total of 113 primary EOC patients, 13 BOT patients, and 728 patients with benign gynecological conditions (including ovarian cysts, endometrioma, teratoma, pelvic inflammatory diseases, adenomyoma, uterine myoma, and pelvic tuberculosis et, al.) were included in this study. IgG Gal-ratio was significantly higher in EOC patients compared to those with BOT or benign conditions (0.69 ± 0.41 vs. 0.38 ± 0.17 vs. 0.30 ± 0.13, p < 0.001). A similar trend was observed in serous BOT (n = 9) compared to benign conditions (0.44 ± 0.17 vs. 0.30 ± 0.13, p = 0.003). IgG Gal-ratio demonstrated comparable performance to CA125 in differentiating ovarian cancer from non-malignant gynecological conditions (AUC = 0.871 vs. 0.872). For early detection, IgG Gal-ratio outperformed CA125 in detecting stage I EOC patients (AUC = 0.835 vs. 0.761). Combination of these two markers (Gal-CA125 = IgG Gal-ratio × CA125) provide higher specificity in detecting stage I ovarian cancer than CA125 alone (59.9% vs. 32.9%) at a fixed sensitivity of 90.0%. The IgG Gal-ratio is a robust serum biomarker for discriminating EOC patients from those with BOT or benign gynecological conditions, offering a promising tool for early detection and diagnosis.