Περίληψη:
CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76–0.92]; lowest tertile: 0.76 [0.67–0.86]; phet = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection. © 2017 UICC
Συγγραφείς:
Fortner, R.T.
Schock, H.
Le Cornet, C.
Hüsing, A.
Vitonis, A.F.
Johnson, T.S.
Fichorova, R.N.
Fashemi, T.
Yamamoto, H.S.
Tjønneland, A.
Hansen, L.
Overvad, K.
Boutron-Ruault, M.-C.
Kvaskoff, M.
Severi, G.
Boeing, H.
Trichopoulou, A.
Papatesta, E.-M.
La Vecchia, C.
Palli, D.
Sieri, S.
Tumino, R.
Sacerdote, C.
Mattiello, A.
Onland-Moret, N.C.
Peeters, P.H.
Bueno-de-Mesquita, H.B.
Weiderpass, E.
Quirós, J.R.
Duell, E.J.
Sánchez, M.-J.
Navarro, C.
Ardanaz, E.
Larrañaga, N.
Nodin, B.
Jirström, K.
Idahl, A.
Lundin, E.
Khaw, K.-T.
Travis, R.C.
Gunter, M.
Johansson, M.
Dossus, L.
Merritt, M.A.
Riboli, E.
Terry, K.L.
Cramer, D.W.
Kaaks, R.
Λέξεις-κλειδιά:
autoantibody; CA 125 antigen; CA125 autoantibody; unclassified drug; autoantibody; CA 125 antigen; membrane protein; MUC16 protein, human; tumor marker, adult; aged; area under the curve; Article; blood sampling; cancer growth; case control study; cohort analysis; controlled study; correlational study; early cancer diagnosis; electrochemiluminescence; female; human; immune response; major clinical study; ovary cancer; priority journal; blood; early cancer diagnosis; immunology; middle aged; ovary tumor; procedures; receiver operating characteristic; sensitivity and specificity, Adult; Aged; Area Under Curve; Autoantibodies; Biomarkers, Tumor; CA-125 Antigen; Case-Control Studies; Cohort Studies; Early Detection of Cancer; Female; Humans; Membrane Proteins; Middle Aged; Ovarian Neoplasms; ROC Curve; Sensitivity and Specificity
