Integrated analysis of circulating and tissue proteomes reveal fibronectin 1 is a potential biomarker in papillary thyroid cancer

Abstract As the most frequent subtype of thyroid cancer, papillary thyroid cancer (PTC) has 20% indeterminate cases from preoperative cytology that could not be accurately diagnosed, which might lead to the surgical removal of the thyroid gland. To address this concern, we executed an in-depth analysis of serum proteomes of 26 PTC patients and 26 healthy controls using antibody microarrays and Data Independent Acquisition Mass Spectrometry (DIA-MS). The results identified a total of 1,091 serum proteins spanning 10–12 orders of magnitude, in which 157 differentially expressed proteins were identified that participate complement activation and coagulation cascades, platelet degranulation pathways. Furthermore, the analysis of serum proteomes before and after surgery indicate that the expression of proteins such as lactate dehydrogenase A, OR52B4 were changed which participate into fibrin clot formation and ECM-receptor interaction pathways. The further analysis of proteomes of PTC and neighboring tissues reveals integrin-mediated pathways that may cross talk between tissue and circulating compartment. Among these cross-talk proteins, circulating fibronectin 1 (FN1), gelsolin (GSN) and UDP-glucose 4-epimerase (GALE) were indicated as promising biomarkers to the PTC identification and validated in an independent cohort. To differentiate patients with benign nodule and PTC, the best ELISA result was from FN1 (sensitivity = 96.89%; specificity = 91.67%) which was tested in an independent cohort. Altogether, our results provide proteomic landscapes of PTC cancer before and after surgery as well as the cross-talk between tissue and circulating system, which would be valuable to understand the PTC pathology and improve PTC diagnostics in future.