Zhaowei Meng1, Jian Tan2, Guizhi Zhang3, Weijun Tian4, Qiang Fu4, Weidong Li4, Xianghui He4, Shuanghu Wu4, Zhiqiang Yang4, Xiaoyu Liang4, Liyan Dong4, Qing Zhang5, Li Liu5, Yujie Zhang6, Ke Xu7, Boning Liu7, Ning Li3, Xue Li3, Qiang Jia3, Yajing He3, Sheng Wang3, Renfei Wang3, Wei Zheng3, Xinghua Song8, Jianping Zhang3, Tianpeng Hu3, Na Liu3, Arun Upadhyaya3. 1. Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China. Electronic address: jamesmencius@163.com. 2. Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China. Electronic address: tanposta@163.com. 3. Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China. 4. Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China. 5. Department of Health Management, Tianjin Medical University General Hospital, Tianjin, PR China. 6. Department of Pathology, Tianjin Medical University General Hospital, Tianjin, PR China. 7. Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, PR China. 8. Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China; Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang Medical University, Hangzhou, PR China.
Abstract
AIMS: Midkine is a multifunctional cytokine identified to be a promising cancer biomarker. We aimed to prospectively investigate serum midkine as a diagnostic and prognostic biomarker in differentiated thyroid cancer (DTC). MAIN METHODS: 162 patients with thyroid nodules participated in the surgical cohort (post-surgical pathology proved 70 cases with DTC and 92 cases with benign thyroid nodules), 75 healthy subjects served as control. Diagnostic values of pre-surgical midkine and thyroglobulin for DTC were conducted by receiver operating characteristic (ROC) curves. 214 DTC patients participated in the (131)I treatment cohort. Prognostic values of pre-(131)I-ablative midkine and thyroglobulin to predict (131)I-avid metastases were performed by ROC curves. Metastasis-free survival was analyzed by the Kaplan-Meier method. KEY FINDINGS: Much better diagnostic capability of midkine than thyroglobulin was shown to differentiate DTC from benign thyroid nodules, with cut-off midkine value of 323.12pg/ml and diagnostic accuracy of 75.31%. Nearly similar diagnostic capabilities of midkine and thyroglobulin were shown to distinguish DTC from normal participants. Pre-(131)I-ablative thyroglobulin demonstrated perfect ability to predict metastases, with cut-off value and diagnostic accuracy of 19.50ng/ml and 96.73%. Midkine also performed well with a cut-off value and diagnostic accuracy of 504.71pg/ml and 89.25%. DTC patients with midkine or thyroglobulin levels higher than those of thresholds (500pg/ml or 20ng/ml) showed a significantly worse (131)I-avid metastasis-free survival by the Kaplan-Meier method (P<0.01). SIGNIFICANCE: Our results show that midkine is as good as or even better than thyroglobulin to screen patients with thyroid nodules for DTC before surgery, and to predict whether metastases exist before the first (131)I ablative therapy.
AIMS: Midkine is a multifunctional cytokine identified to be a promising cancer biomarker. We aimed to prospectively investigate serum midkine as a diagnostic and prognostic biomarker in differentiated thyroid cancer (DTC). MAIN METHODS: 162 patients with thyroid nodules participated in the surgical cohort (post-surgical pathology proved 70 cases with DTC and 92 cases with benign thyroid nodules), 75 healthy subjects served as control. Diagnostic values of pre-surgical midkine and thyroglobulin for DTC were conducted by receiver operating characteristic (ROC) curves. 214 DTCpatients participated in the (131)I treatment cohort. Prognostic values of pre-(131)I-ablative midkine and thyroglobulin to predict (131)I-avid metastases were performed by ROC curves. Metastasis-free survival was analyzed by the Kaplan-Meier method. KEY FINDINGS: Much better diagnostic capability of midkine than thyroglobulin was shown to differentiate DTC from benign thyroid nodules, with cut-off midkine value of 323.12pg/ml and diagnostic accuracy of 75.31%. Nearly similar diagnostic capabilities of midkine and thyroglobulin were shown to distinguish DTC from normal participants. Pre-(131)I-ablative thyroglobulin demonstrated perfect ability to predict metastases, with cut-off value and diagnostic accuracy of 19.50ng/ml and 96.73%. Midkine also performed well with a cut-off value and diagnostic accuracy of 504.71pg/ml and 89.25%. DTCpatients with midkine or thyroglobulin levels higher than those of thresholds (500pg/ml or 20ng/ml) showed a significantly worse (131)I-avid metastasis-free survival by the Kaplan-Meier method (P<0.01). SIGNIFICANCE: Our results show that midkine is as good as or even better than thyroglobulin to screen patients with thyroid nodules for DTC before surgery, and to predict whether metastases exist before the first (131)I ablative therapy.
Authors: Tamina Rawnaq-Möllers; Tarik Ghadban; Louisa Stern; Erik Mueller; Eugen Bellon; Matthias Reeh; Rainer Grotelueschen; Cenap Guengoer; Nathaniel Melling; Mara Goetz; Daniel R Perez; Jakob R Izbicki Journal: Sci Rep Date: 2021-07-16 Impact factor: 4.379