A1 Refereed original research article in a scientific journal

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




AuthorsJain Shruti, Parimelazhagan Santhi Priyadharshini, Vinod Rufus, Afrin Ruma Shamima, Huhtinen Kaisa, Pettersson Kim, Sundfeldt Karin, Leivo Janne, Gidwani Kamlesh

PublisherElsevier B.V.

Publication year2023

JournalClinica Chimica Acta

Journal name in sourceClinica Chimica Acta

Article number117323

Volume543

eISSN1873-3492

DOIhttps://doi.org/10.1016/j.cca.2023.117323

Web address https://www.sciencedirect.com/science/article/pii/S0009898123001250

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/179258314


Abstract

Background
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.

Methods
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).

Results
Sialylated Tn antibody based glycovariants of ITGα3 (ITGα3STn) and CD63 (CD63STn) performed better
than corresponding protein epitope-based immunoassays, ITGα3IA and CD63IA respectively. Combined ITGα3 based assays (ITGα3IA + ITGα3STn) detected 49 out of 55 malignant & borderline cases without detecting any of the 22 benign and healthy cysts.

Conclusion
Our findings indicate the potential diagnostic application of ITGα3STn along with total ITGα3IA, which
could help reduce the unnecessary surgeries. The results encourage studying further the potential use of these novel assays to detect EOC at earlier clinical stages.


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