Dysregulation of microRNAs as the risk factor of lymph node metastasis in papillary thyroid carcinoma: systematic review

Papillary thyroid carcinoma (PTC) has an excellent prognosis with a relatively low mortality rate, but a small portion of PTC patients suffer from an aggressive form of the disease. In such cases early detection of lymph node metastasis (LNM) is as paramount as it is problematic. The routine use of central neck lymph node dissection is not recommended. New methods to detect LNM are needed. MicroRNAs are a potential biomarker for diagnosis and prognosis of PTC. In this review we summarise the current knowledge regarding dysregulated miRNAs and their association with LNM in PTS patients. The PubMed and EBSCO databases were searched using terms for "microRNA", "thyroid carcinoma", and "prognosis" by using Boolean operators. Based on eligibility and exclusion criteria, articles were screened and reviewed in full, methodological data of included studies were extracted, and risk of bias analysis performed. In total, 446 unique studies were extracted from the mentioned databases, and based on inclusion and exclusion criteria 27 studies were included in this review. Of them 17 analysed tissue microRNAs, 5 analysed circulating microRNAs, and 5 studies analysed both tissue and circulating samples. MiRNA-146B, miRNA-221, miRNA-222, miRNA-21, miRNA-204, miRNA-451, miRNA-199a-3p, and miRNA-30a-3p were dysregulated in at least 2 separate studies. A sizable portion of studies failed to show statistically significant differences in miRNA expression between LNM-positive and -negative patients. Different methodologies and disparities of patient populations could explain these discrepancies.\ This research supports the statement that specific up- and downregulated miRNAs are associated with LNM in PTC patients. However, the prognostic value of these miRNAs is limited. Additional targeted cohort studies are required to elucidate the role of miRNAs in defining individualised treatment strategies for thyroid cancer patients.