Autoantibody to Tumor Antigen, Alpha 2-HS Glycoprotein: A Novel Biomarker of Breast Cancer Screening and Diagnosis

We sought to identify a new serum biomarker for breast cancer screening and diagnosis using stepwise proteomic analysis of sera from breast cancer patients to detect the presence of autoantibodies that react with urinary protein. Two-dimensional immunoblotting was done for screening autoimmunogenic tumor antigens in the urine of breast cancer patients. Reactive spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Among urinary proteins separated by two-dimensional electrophoresis, 13 spots showed strong reactivity with pooled sera from breast cancer patients or control sera. By mass spectrometry, we identified alpha 2-HS glycoprotein (AHSG) as a tumor antigen. Peripheral blood was obtained from 81 women diagnosed with breast cancer before surgery and 73 female donors without evidence of any malignancy for the individual analysis. In one-dimensional Western blot analysis, AHSG autoantibody was detected in 64 of 81 breast cancer patients (79.1%) and in 7 of 73 controls (9.6%). The sensitivity of this test in breast cancer patients was 79.0%. Our results suggest that AHSG and anti-AHSG autoantibody may be useful serum biomarkers for breast cancer screening and diagnosis.Chang JW, 2008, PROTEOM CLIN APPL, V2, P23, DOI 10.1002/prca.200780049Harris L, 2007, J CLIN ONCOL, V25, P5287, DOI 10.1200/JCO.2007.14.2364Caron M, 2007, MOL CELL PROTEOMICS, V6, P1115, DOI 10.1074/mcp.R600016-MCP200Hu S, 2006, PROTEOMICS, V6, P6326, DOI 10.1002/pmic.200600284Fujita Y, 2006, CLIN CANCER RES, V12, P6415, DOI 10.1158/1078-0432.CCR-06-1315Downes MR, 2006, BIOMARKERS, V11, P406, DOI 10.1080/13547500600799821Chang JW, 2005, FEBS LETT, V579, P2873, DOI 10.1016/j.febslet.2005.04.028Canelle L, 2005, J IMMUNOL METHODS, V299, P77, DOI 10.1016/j.jim.2005.01.015Molina R, 2005, TUMOR BIOL, V26, P281, DOI 10.1159/000089260Swallow CJ, 2004, CANCER RES, V64, P6402Carlsson L, 2004, J ANDROL, V25, P699Hong SH, 2004, CANCER RES, V64, P5504Hutchinson JN, 2004, CANCER RES, V64, P3171Pieper R, 2004, PROTEOMICS, V4, P1159, DOI 10.1002/pmic.200300661Mocellin S, 2003, BBA-REV CANCER, V1653, P61, DOI 10.1016/S0304-419X(03)00032-5Wilson KS, 2002, AM J PATHOL, V161, P1171Szweras M, 2002, J BIOL CHEM, V277, P19991, DOI 10.1074/jbc.M112234200Volkmann M, 2002, ONCOLOGY-BASEL, V63, P297, DOI 10.1159/000065472Sugi T, 2002, J REPROD IMMUNOL, V53, P269Le Naour F, 2001, CLIN CANCER RES, V7, P3328Brichory FM, 2001, P NATL ACAD SCI USA, V98, P9824Bosscher JR, 2001, GYNECOL ONCOL, V81, P138Gion M, 2001, EUR J CANCER, V37, P355Mathews ST, 2000, MOL CELL ENDOCRINOL, V164, P87Chen SH, 2000, FASEB J, V14, P565Menard S, 2000, J CELL PHYSIOL, V182, P150METCALFE S, 2000, BREAST CANCER RES, V2, P438Duffy MJ, 1999, ANN CLIN BIOCHEM, V36, P579Lenner P, 1999, BRIT J CANCER, V79, P927Wang HC, 1998, P NATL ACAD SCI USA, V95, P14429Molina R, 1998, BREAST CANCER RES TR, V51, P109Conroy SE, 1998, EUR J CANCER, V34, P942Disis ML, 1997, J CLIN ONCOL, V15, P3363Disis ML, 1997, ADV CANCER RES, V71, P343Chu KC, 1996, J NATL CANCER I, V88, P1571Bast RC, 1996, J CLIN ONCOL, V14, P2843vonMensdorffPouilly S, 1996, EUR J CANCER, V32A, P1325vanDalen A, 1996, ANTICANCER RES, V16, P2345MADIGAN MP, 1995, J NATL CANCER I, V87, P1681GOUREVITCH MM, 1995, BRIT J CANCER, V72, P934SRINIVAS PR, 1993, MOL ENDOCRINOL, V7, P1445JAMEEL A, 1992, INT J CANCER, V50, P409DNISTRIAN AM, 1991, TUMOR BIOL, V12, P82VANDALEN A, 1990, TUMOR BIOL, V11, P189TABAR L, 1985, LANCET, V1, P829ANDERSON L, 1977, P NATL ACAD SCI USA, V74, P54211