supplementary figures 1-10. Supplementary Figure 1 - Representative array images for "ring" structure surrounding spots. Supplementary Figure 2 - Array screening reproducibility. Supplementary Figure 3 - AAb response counts per sample are similar between BLBC and controls. Supplementary Figure 4 - GSEA analysis of AAb targets identified by either visual analysis. Supplementary Figure 5 - GSEA analysis of AAb protein targets against their biochemical properties. Supplementary Figure 6 - GO cellular component analysis. Supplementary Figure 7 - Heatmap of plasma AAb responses against selected proteins based on quantitative analysis in sample set 1 (basal-like, n=45; controls, n=45). Supplementary Figure 8 - Heatmap of plasma AAb responses against selected proteins based on visual image analysis in sample set 1 (basal-like, n=45; controls, n=45). Supplementary Figure 9 - mRNA expression levels of candidate biomarkers in breast invasive carcinoma grouped by subtypes (TCGA). Supplementary Figure 10 - Overall survival of BLBC patients stratified by AAb responses.
ARTICLE ABSTRACT
Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease.Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case–control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed.Results: We identified 13 AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (P = 0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival [MN1 AAb marker HR = 2.25, 95% confidence interval (CI), 1.03–4.91; P = 0.04; TP53, HR = 2.02, 95% CI, 1.06–3.85; P = 0.03]. We found limited evidence that AAb levels differed by demographic characteristics.Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection.Impact: Our study identifies 13 AAb markers associated specifically with BLBC and may improve detection or management of this deadly disease. Cancer Epidemiol Biomarkers Prev; 24(9); 1332–40. ©2015 AACR.
