Diagnostic potential of nanoparticle aided assays for MUC16 and MUC1 glycovariants in ovarian cancer

• Published in: International journal of cancer 2022-10, Vol.151 (7), p.1175-1184
• Main Authors: Jain, Shruti, Nadeem, Nimrah, Ulfenborg, Benjamin, Mäkelä, Maria, Ruma, Shamima Afrin, Terävä, Joonas, Huhtinen, Kaisa, Leivo, Janne, Kristjansdottir, Björg, Pettersson, Kim, Sundfeldt, Karin, Gidwani, Kamlesh
• Format: Article
• Language: English
• Subjects: Bioinformatics; Bioinformatik; biomarkers; ca125; Cancer; Cancer and Oncology; Cancer och onkologi; Cysts; diagnosis; epithelial ovarian cancer; europium nanoparticle; expression; glycans; he-4; Medical research; mucins; Nanoparticles; Oncology; Ovarian cancer; Ovarian carcinoma; Post-menopause; protein glycosylation; STn
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.34111

Our study reports the discovery and evaluation of nanoparticle aided sensitive assays for glycovariants of MUC16 and MUC1 in a unique collection of paired ovarian cyst fluids and serum samples obtained at or prior to surgery for ovarian carcinoma suspicion. Selected glycovariants and the immunoassays for CA125, CA15‐3 and HE4 were compared and validated in 347 cyst fluid and serum samples. Whereas CA125 and CA15‐3 performed poorly in cyst fluid to separate carcinoma and controls, four glycovariants including MUC16MGL, MUC16STn, MUC1STn and MUC1Tn provided highly improved separations. In serum, the two STn glycovariants outperformed conventional CA125, CA15‐3 and HE4 assays in all subcategories analyzed with main benefits obtained at high specificities and at postmenopausal and early‐stage disease. Serum MUC16STn performed best at high specificity (90%‐99%), but sensitivity was also improved by the other glycovariants and CA15‐3. The highly improved specificity, excellent analytical sensitivity and robustness of the nanoparticle assisted glycovariant assays carry great promise for improved identification and early detection of ovarian carcinoma in routine differential diagnostics. What's new? While MUC16 represents a promising serum marker for epithelial ovarian cancer, its inadequate specificity has impeded clinical applications. Our study using a novel immunoassay with fluorescent nanoparticles coated with glycan structure‐specific binders shows that cancerous sub‐forms of MUC16 and MUC1 can be quantitated while suppressing mucin signals from confounding benign conditions. In ovarian cyst fluids, immunoassays for MUC16 and MUC1 STn glycovariants were superior to conventional CA125 and CA15‐3 immunoassays. In paired serum samples, the main benefits were seen in postmenopausal and early‐stage patients. The results pave the way for improved routine differential diagnostics of epithelial ovarian cancer.