Survey of autoantibody responses against tumor-associated antigens in thyroid cancer

BACKGROUND: Autoantibodies against tumor-associated antigens (TAAs) have been shown to serve as highly specific serological biomarkers for the diagnosis of various solid cancers. Although the autoimmunity against thyroid tissue specific antigens has been studied extensively, so far, the autoantibody responses against common TAAs such as cancer-testis antigens (CTAs), mutated or differentiation antigens have not been comprehensively analyzed in patients with thyroid cancer. OBJECTIVE: The current study aims to characterize the frequency of autoantibody responses against common TAAs in patients with thyroid cancer and benign thyroid nodules. METHODS: A phage-displayed antigen microarray comprising 65 TAAs was produced and tested with sera from 53 patients with thyroid cancer, 90 patients with benign thyroid nodules and 96 cancer-free individuals, 100 melanoma, 54 breast cancer and 14 lung cancer patients as controls. RESULTS: A panel of 6 TAAs was identified that preferentially reacted with sera from patients with thyroid cancer. The top ranked antigen in this panel was GAGE1 eliciting autoantibody response in 6% of patients with thyroid cancer but not with benign nodules, whereas no reactivity to other CTAs was detected in the sera from patients with thyroid cancer. CONCLUSIONS: Although six TAAs, including one CTA, showed thyroid cancer-associated reactivity, overall, spontaneous humoral immune responses against TAAs are rare in thyroid cancer and their utility for the development of non-invasive assay for the differential diagnosis of thyroid nodules is limited.