Shruti Jain

Aberrant glycosylation of α3 integrins as diagnostic markers in epithelial ovarian cancer

Glycans are strongly involved in stability and function of integrins (ITG) and tetraspanin protein CD63 and their respective interaction partners as they are dysregulated in the tumorigenic processes. Glycosylation changes is a universal phenomenon of cancer cells. In this study, glycosylation changes in epithelial ovarian cancer (EOC) are explored using tetraspanin and integrin molecules. ITG and CD63 were immobilized from 10 EOC and 5 benign ovarian cyst fluid on microtiter wells and traced with 3 glycan binding proteins (STn, WGA, UEA) conjugated on europium nanoparticles. Total protein measurements (ITG & CD63 immunoassays) were also performed. The most promising glycovariant candidates identified were then clinically evaluated on the whole cohort of 77 ovarian cyst fluids. Additional testing was performed in ascites fluid samples of liver cirrhosis (n = 2) and EOC (n = 4). Sialylated Tn antibody based glycovariants of ITGα3 (ITGα3 Our findings indicate the potential diagnostic application of ITGα3

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

AbstractOur 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.