High-throughput assessment of the antibody profile in ovarian cancer ascitic fluids

Frank Antony, Cecilia Deantonio, Diego Cotella, Maria Felicia Soluri, Olga Tarasiuk, Francesco Raspagliesi, Fulvio Adorni, Silvano Piazza, Yari Ciani, Claudio Santoro, Paolo Macor, Delia Mezzanzanica, Daniele Sblattero

Research output: Contribution to journalArticle

Abstract

The identification of effective biomarkers for early diagnosis, prognosis, and response to treatments remains a challenge in ovarian cancer (OC) research. Here, we present an unbiased high-throughput approach to profile ascitic fluid autoantibodies in order to obtain a tumor-specific antigen signature in OC. We first reported the reactivity of immunoglobulins (Igs) purified from OC patient ascites towards two different OC cell lines. Using a discovery set of Igs, we selected tumor-specific antigens from a phage display cDNA library. After biopanning, 700 proteins were expressed as fusion protein and used in protein array to enable large-scale immunoscreening with independent sets of cancer and noncancerous control. Finally, the selected antigens were validated by ELISA. The initial screening identified eight antigenic clones: CREB3, MRPL46, EXOSC10, BCOR, HMGN2, HIP1R, OLFM4, and KIAA1755. These antigens were all validated by ELISA in a study involving ascitic Igs from 153 patients (69 with OC, 34 with other cancers and 50 without cancer), with CREB3 showing the highest sensitivity (86.95%) and specificity (98%). Notably, we were able to identify an association between the tumor-associated (TA) antibody response and the response to a first-line tumor treatment (platinum-based chemotherapy). A stronger association was found by combining three antigens (BCOR, CREB3, and MRLP46) as a single antibody signature. Measurement of an ascitic fluid antibody response to multiple TA antigens may aid in the identification of new prognostic signatures in OC patients and shift attention to new potentially relevant targets.

Original languageEnglish
Article numbere1614856
JournalOncoImmunology
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 2 2019

Keywords

  • ascite
  • biomarker
  • Ovarian cancer
  • protein microarray
  • tumor-associated antigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Fingerprint Dive into the research topics of 'High-throughput assessment of the antibody profile in ovarian cancer ascitic fluids'. Together they form a unique fingerprint.

  • Cite this

    Antony, F., Deantonio, C., Cotella, D., Soluri, M. F., Tarasiuk, O., Raspagliesi, F., Adorni, F., Piazza, S., Ciani, Y., Santoro, C., Macor, P., Mezzanzanica, D., & Sblattero, D. (2019). High-throughput assessment of the antibody profile in ovarian cancer ascitic fluids. OncoImmunology, 8(9), [e1614856]. https://doi.org/10.1080/2162402X.2019.1614856