Nuove frontiere nel carcinoma midollare della tiroide: identificazione di nuovi biomarkers diagnostici

Background: medullary thyroid carcinoma (MTC) is rare thyroid cancer. The difficulty in management and the unfavorable outcome are mainly due to the absence of tools for early diagnosis. Recent studies have demonstrated the deregulation of microRNAs (miRNAs) in tumor samples from MTC patients. Extracellular plasma vesicles (pEVs) containing miRNA represent an emerging source of tumor biomarkers. There are no data from the circulating pEV-miRNAs in patients with MTC. Aim: to identify new circulating diagnostic biomarkers in MTC. Study design: multicenter, prospective, observational study enrolling adult patients with stage I-IV MTC (Group 1, n=23), compared to healthy subjects (Group 2, n=22). For Group 1 patients we collected: blood sample at the time of surgery and tumor tissue from the primary tumor. Step 1: pre-operative plasma from MTC patients (Group 1a) was compared to plasma from healthy subjects (Group 2). Step 2: pre-operative plasma from each MTC patients (Group 1a) was compared to tumor tissue of the same patient (Group 1b). Step 3: data from Step 1 and Step 2 were combined. Methods: the expression analysis of circulating (pEV) and tissue miRNAs was performed by RT-qPCR with TLDA technology analyzing 754 miRNAs. Results were considered statistically significant when P-values were <0.05 Results: 555 miRNAs are considered to be informative comparing Group 1a and Group 2, 44 of them differentially expressed between two groups. 603 miRNAs are considered to be informative, comparing Group 1a vs Group 1b, 209 of them differentially expressed and 394 equally expressed between two groups, respectively. Combining Step 1 and Step 2 results, 24 miRNAs were identified. Conclusions: a specific pattern of pEV-miRNAs was observed in MTC patients, which in part reflects tissue miRNAs arrangement. The 24 miRNAs identified represent potential diagnostic biomarkers in MTC, that could play an active role in the modulation of cellular pathways in targeted cells.