title: Multiplex determination of serological signatures in the sera of colorectal cancer patients using hydrogel biochips.
abstract: Colorectal cancer (CRC) is the third most common malignancy in industrialized countries. Despite the advances in diagnostics and development of new drugs, the 5-year survival remains only 60-65%. Our approach to early diagnostics of CRC is based on the determination of serological signatures with an array of hemispherical hydrogel cells containing immobilized proteins and oligosaccharides (glycochip). The compounds immobilized on the glycochip include tumor-associated glycans (SiaTn, Tn, TF, Le(C) , Le(Y) , SiaLe(A) , and Manβ1-4GlcNAcβ) and antibodies against human immunoglobulins IgG, IgA, and IgM. The glycochip detects antibodies against tumor-associated glycans in patients' sera. The simultaneous measurement of the levels of immunoglobulins enhances the diagnostic impact of the signatures. In this work, we found previously unreported increase in antibodies against oligosaccharide Manβ1-4GlcNAcβ in patients with CRC. In parallel with these experiments, we determined the levels of oncomarkers carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA 125, CA 15-3, human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) using another gel-based biochip with immobilized antibodies (oncochip) developed earlier in our laboratory. In total, 69 samples from healthy donors, 33 from patients with colorectal carcinoma, and 27 from patients with inflammatory bowel diseases were studied. The use of combined signatures of antiglycan antibodies and oncomarkers provides much better predictive value than the conventional measurement of oncomarkers CEA and CA 19-9. Positive predictive value of CRC diagnoses using together glycochip and oncochip reached 95% with the sensitivity and specificity 88% and 98%, respectively. Thus, the combination of antibody profiling with detection of conventional oncomarkers proved to be a promising tool in diagnostics of CRC.
authors.affiliation: Engelhardt Institute of Molecular Biology (IMB RAS), Russian Academy of Sciences, Moscow, Russia.
authors.forename: Veronika I
authors.initials: VI
authors.lastname: Butvilovskaya
authors.affiliation: Engelhardt Institute of Molecular Biology (IMB RAS), Russian Academy of Sciences, Moscow, Russia.
authors.forename: Sofya B
authors.initials: SB
authors.lastname: Popletaeva
authors.affiliation: Engelhardt Institute of Molecular Biology (IMB RAS), Russian Academy of Sciences, Moscow, Russia.
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Chechetkin
authors.affiliation: Moscow Institute of Physics and Technology (State University), Moscow, Russia.
authors.forename: Zhanna I
authors.initials: ZI
authors.lastname: Zubtsova
authors.affiliation: Engelhardt Institute of Molecular Biology (IMB RAS), Russian Academy of Sciences, Moscow, Russia.
authors.forename: Marya V
authors.initials: MV
authors.lastname: Tsybulskaya
authors.affiliation: V. M. Petrovsky Russian Center of Science and Surgery, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Larisa O
authors.initials: LO
authors.lastname: Samokhina
authors.affiliation: V. M. Petrovsky Russian Center of Science and Surgery, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Leonid I
authors.initials: LI
authors.lastname: Vinnitskii
authors.affiliation: V. M. Petrovsky Russian Center of Science and Surgery, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Aligeydar A
authors.initials: AA
authors.lastname: Ragimov
authors.affiliation: Moscow City Clinical Hospital No. 12, Russia.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Pozharitskaya
authors.affiliation: I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
authors.forename: Galina A
authors.initials: GA
authors.lastname: Grigor Eva
authors.affiliation: I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
authors.forename: Natalya Y
authors.initials: NY
authors.lastname: Meshalkina
authors.affiliation: I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Golysheva
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Shilova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Nicolai V
authors.initials: NV
authors.lastname: Bovin
authors.affiliation: Engelhardt Institute of Molecular Biology (IMB RAS), Russian Academy of Sciences, Moscow, Russia.
authors.forename: Aleksander S
authors.initials: AS
authors.lastname: Zasedatelev
authors.affiliation: Engelhardt Institute of Molecular Biology (IMB RAS), Russian Academy of Sciences, Moscow, Russia.
authors.forename: Alla Y
authors.initials: AY
authors.lastname: Rubina
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011134:Polysaccharides / Q000276:immunology; D040081:Protein Array Analysis / Q000379:methods; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D011134:Polysaccharides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: Colorectal cancer; hydrogel biochips; tumor antibodies; tumor markers; tumor-associated glycans