Identification and validation of new autoantibodies for the diagnosis of DCIS and node negative early-stage breast cancers
Jérôme Lacombe
Department of Cellular Biology, CHU Montpellier, Arnaud de Villeneuve, Montpellier, France
Department of Medicine, University of Montpellier I, Montpellier, France
CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France
J.L. and A.M. contributed equally to this work
Search for more papers by this authorAlain Mangé
Department of Cellular Biology, CHU Montpellier, Arnaud de Villeneuve, Montpellier, France
Department of Medicine, University of Montpellier I, Montpellier, France
CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France
J.L. and A.M. contributed equally to this work
Search for more papers by this authorMarta Jarlier
CRLC Val d'Aurelle, Department of Biostatistics, Montpellier, France
Search for more papers by this authorCaroline Bascoul-Mollevi
CRLC Val d'Aurelle, Department of Biostatistics, Montpellier, France
Search for more papers by this authorPhilippe Rouanet
CRLC Val d'Aurelle, Department of Surgery, Montpellier, France
Search for more papers by this authorPierre-Jean Lamy
CRLC Val d'Aurelle, Department of Biology, Montpellier, France
Search for more papers by this authorThierry Maudelonde
Department of Cellular Biology, CHU Montpellier, Arnaud de Villeneuve, Montpellier, France
Department of Medicine, University of Montpellier I, Montpellier, France
CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France
Search for more papers by this authorCorresponding Author
Jérôme Solassol
Department of Cellular Biology, CHU Montpellier, Arnaud de Villeneuve, Montpellier, France
Department of Medicine, University of Montpellier I, Montpellier, France
CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France
Tel.: 33-4-67-61-24-12, Fax: 33-4-67-33-95-90
Batiment de recherche du CRLC Val d'Aurelle, 208 rue des Apothicaires, 34298 Montpellier Cedex 5, FranceSearch for more papers by this authorJérôme Lacombe
Department of Cellular Biology, CHU Montpellier, Arnaud de Villeneuve, Montpellier, France
Department of Medicine, University of Montpellier I, Montpellier, France
CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France
J.L. and A.M. contributed equally to this work
Search for more papers by this authorAlain Mangé
Department of Cellular Biology, CHU Montpellier, Arnaud de Villeneuve, Montpellier, France
Department of Medicine, University of Montpellier I, Montpellier, France
CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France
J.L. and A.M. contributed equally to this work
Search for more papers by this authorMarta Jarlier
CRLC Val d'Aurelle, Department of Biostatistics, Montpellier, France
Search for more papers by this authorCaroline Bascoul-Mollevi
CRLC Val d'Aurelle, Department of Biostatistics, Montpellier, France
Search for more papers by this authorPhilippe Rouanet
CRLC Val d'Aurelle, Department of Surgery, Montpellier, France
Search for more papers by this authorPierre-Jean Lamy
CRLC Val d'Aurelle, Department of Biology, Montpellier, France
Search for more papers by this authorThierry Maudelonde
Department of Cellular Biology, CHU Montpellier, Arnaud de Villeneuve, Montpellier, France
Department of Medicine, University of Montpellier I, Montpellier, France
CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France
Search for more papers by this authorCorresponding Author
Jérôme Solassol
Department of Cellular Biology, CHU Montpellier, Arnaud de Villeneuve, Montpellier, France
Department of Medicine, University of Montpellier I, Montpellier, France
CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France
Tel.: 33-4-67-61-24-12, Fax: 33-4-67-33-95-90
Batiment de recherche du CRLC Val d'Aurelle, 208 rue des Apothicaires, 34298 Montpellier Cedex 5, FranceSearch for more papers by this authorAbstract
Evidence of circulating autoantibodies in cancer patient sera has created opportunities for exploiting them as biomarkers. We report the identification and the clinical validation of an autoantibody panel in newly diagnosed patients with early-stage breast cancer. Proteomic approach and serological screening of a discovery set of sera (n = 80) were performed to identify tumor-associated antigens (TAAs). Autoantibody levels were then measured in an independent validation set (n = 182) against a panel of five TAAs by enzyme-linked immunosorbent assay. Sixty-seven antigens that elicited a specific humoral response in breast cancer were identified and five antigens (GAL3, PAK2, PHB2, RACK1 and RUVBL1) were selected for validation. GAL3 and RACK1 showed significantly increased reactivity in early-stage breast cancer. When combined, the five markers significantly discriminated early-stage cancer from healthy individuals (AUC = 0.81; 95% CI [0.74–0.86]). Interestingly, this value was high in both node-negative early-stage primary breast cancer (AUC = 0.81; 95% CI [0.72–0.88]) and ductal carcinoma in situ (AUC = 0.85; 95% CI [0.76–0.95]) populations. This autoantibody panel could be useful as a diagnostic tool in a screening strategy of early-stage invasive breast cancer and preinvasive breast cancer. It could be particularly appropriate in complement to mammography for women with high breast density.
Abstract
What's new?
This study shows the clinical relevance of a combination of five antigens as a blood-screening test for early breast cancer detection. The antigens were identified using a proteomic approach and validated in an independent cohort of 182 samples by ELISA. Since the effectiveness of mammographic screening declines in cohorts of patients with dense breast tissue and small lesions, testing for the status of this biomarker panel may help improve the detection of early-stage cancer in women.
Supporting Information
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