Integrated analysis of circulating and tissue proteomes reveals that fibronectin 1 is a potential biomarker in papillary thyroid cancer
Guochao Ye,
Xiaomei Zhang,
Mansheng Li,
Zixiang Lin,
Yongcan Xu,
Haoru Dong,
Jie Zhou,
Jiaqi Zhang,
Sheng Wang,
Yunping Zhu,
Xiaobo Yu,
Xu Qian
Affiliations
Guochao Ye
Department of General Surgery, Huzhou Central Hospital
Xiaomei Zhang
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics
Mansheng Li
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics
Zixiang Lin
School of Basic Medical Sciences, Peking University
Yongcan Xu
Department of General Surgery, Huzhou Central Hospital
Haoru Dong
Department of Clinical Laboratory, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), The Chinese Academy of Sciences
Jie Zhou
Department of Clinical Laboratory, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), The Chinese Academy of Sciences
Jiaqi Zhang
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics
Sheng Wang
Department of Clinical Laboratory, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), The Chinese Academy of Sciences
Yunping Zhu
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics
Xiaobo Yu
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics
Xu Qian
Department of Clinical Laboratory, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), The Chinese Academy of Sciences
Abstract Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid cancer, but 20% of cases are indeterminate (i.e., cannot be accurately diagnosed) based on preoperative cytology, which might lead to surgical removal of a normal thyroid gland. To address this concern, we performed an in-depth analysis of the serum proteomes of 26 PTC patients and 23 healthy controls using antibody microarrays and data-independent acquisition mass spectrometry (DIA-MS). We identified a total of 1091 serum proteins spanning 10–12 orders of magnitude. 166 differentially expressed proteins were identified that participate in complement activation, coagulation cascades, and platelet degranulation pathways. Furthermore, the analysis of serum proteomes before and after surgery indicated that the expression of proteins such as lactate dehydrogenase A and olfactory receptor family 52 subfamily B member 4, which participate in fibrin clot formation and extracellular matrix-receptor interaction pathways, were changed. Further analysis of the proteomes of PTC and neighboring tissues revealed integrin-mediated pathways with possible crosstalk between the tissue and circulating compartments. Among these cross-talk proteins, circulating fibronectin 1 (FN1), gelsolin (GSN) and UDP-glucose 4-epimerase (GALE) were indicated as promising biomarkers for PTC identification and validated in an independent cohort. In differentiating between patients with benign nodules or PTC, FN1 produced the best ELISA result (sensitivity = 96.89%, specificity = 91.67%). Overall, our results present proteomic landscapes of PTC before and after surgery as well as the crosstalk between tissue and the circulatory system, which is valuable to understand PTC pathology and improve PTC diagnostics in the future.
