Autoantibodies in Breast Cancer Identify Proteins Involved in Self- Renewal and Epigenetic Chromatin Remodeling

Recent studies have shown that autoantibodies developing in cancer patients are tumor-associated and are promising biomarkers for the diagnosis and prognosis of cancer. Here we report a panel of signal transduction molecules with partial sequences identical to the oncogene Bmi-1, NIFK, a nucleolar protein interacting with the FHA domain of Ki- 67, TAB182, a protein interacting with tankyrase-1, CNOT6L, a subunit of the CCR4-NOT complex and to Elp3, a subunit of the elongator complex that are recognized as autoantigens by breast cancer sera with the ability to discriminate between invasive breast cancer and normal sera with high sensitivity and specificity. The proteins bearing the epitopes recognized by these antibodies have conserved regions involved in protein-protein interactions participating in regulatory processes such as self renewal, cell proliferation and survival, chromatin modulation, transcriptional silencing and organ patterning, usually ascribed to stem cell function. In this work we demonstrate by autoantigen microarray analysis that autoantibodies in breast cancer sera have the potential to delineate pathway connectivity. Our data indicate that several pathways involved in maintaining telomere stability are the target of an autoimmune reaction in breast cancer. These find- ings suggest that autoantibodies with the ability to recognize autoantigens involved in self-renewal and epigenetic chro- matin remodeling have the potential to predict an invasive tendency of breast cancer.