title: Evaluation of serum midkine as a biomarker in differentiated thyroid cancer.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China. Electronic address: jamesmencius@163.com.
authors: Zhaowei
authors: Z
authors: Meng
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China. Electronic address: tanposta@163.com.
authors: Jian
authors: J
authors: Tan
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Guizhi
authors: G
authors: Zhang
authors: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Weijun
authors: W
authors: Tian
authors: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Qiang
authors: Q
authors: Fu
authors: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Weidong
authors: W
authors: Li
authors: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Xianghui
authors: X
authors: He
authors: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Shuanghu
authors: S
authors: Wu
authors: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Zhiqiang
authors: Z
authors: Yang
authors: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Xiaoyu
authors: X
authors: Liang
authors: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Liyan
authors: L
authors: Dong
authors: Department of Health Management, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Qing
authors: Q
authors: Zhang
authors: Department of Health Management, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Li
authors: L
authors: Liu
authors: Department of Pathology, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Yujie
authors: Y
authors: Zhang
authors: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Ke
authors: K
authors: Xu
authors: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Boning
authors: B
authors: Liu
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Ning
authors: N
authors: Li
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Xue
authors: X
authors: Li
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Qiang
authors: Q
authors: Jia
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Yajing
authors: Y
authors: He
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Sheng
authors: S
authors: Wang
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Renfei
authors: R
authors: Wang
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Wei
authors: W
authors: Zheng
authors: 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.
authors: Xinghua
authors: X
authors: Song
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Jianping
authors: J
authors: Zhang
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Tianpeng
authors: T
authors: Hu
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Na
authors: N
authors: Liu
authors: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, PR China.
authors: Arun
authors: A
authors: Upadhyaya
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D000078792:Midkine; D011379:Prognosis; D011446:Prospective Studies; D013954:Thyroglobulin / Q000097:blood*; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000473:pathology; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D000078792:Midkine; D013954:Thyroglobulin
keywords: (131)I treatment; Differentiated thyroid cancer (DTC); Kaplan–Meier analysis method; Midkine (MK); Receiver operating characteristic (ROC) curves; Thyroglobulin (Tg)