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Serum thyroglobulin (Tg) is the main post-operative tumor biomarker for patients with differentiated thyroid cancer (DTC). However, the presence of thyroglobulin antibodies (TgAb) can interfere with Tg level and invalidate the test. In this study, we aimed to investigate the predicative value of midkine (MK) as a cancer biomarker for DTC patients with positive TgAb before the first  131 I therapy. MK levels were measured by enzyme-linked immunosorbent assay in 151 recruited DTC patients after exercising strict inclusion and exclusion criteria. There were 28 TgAb positive DTC patients with metastases and 123 DTC patients without metastases. The value of pre- 131 I-ablative MK to predict metastasis was assessed by receiver operating characteristic (ROC) curves in these two groups of patients. MK levels in the TgAb positive DTC patients were significantly higher than the DTC patients without metastases. ROC showed good predictability of MK, with an area under the curve of 0.856 (P < 0.001), and a diagnostic accuracy of 83% at the optimal cut-off value of 550 pg/ml. In conclusion, we show that MK can potentially be used as a surrogate biomarker for predicting DTC metastases when Tg is not suitable due to TgAb positivity.

Serum midkine as a surrogate biomarker for metastatic prediction in differentiated thyroid cancer patients with positive thyroglobulin antibody