Objective: Lymph node metastasis (LNM) is one of the difficulties in the treatment of papillary thyroid carcinoma (PTC). To improve the early detection of PTC LNM and search for novel biomarkers, we carried out plasma-derived exosomal microRNAs studies to identify candidate differentially expressed (DE) exosome-derived miRNAs (Ex- miRNAs) as diagnostic biomarkers in several plasma samples from LNM subjects and patients without LNM.
Methods: From January 2022 to October 2022, 10 plasma samples from patients with thyroid papillary carcinoma diagnosed pathologically after surgery were involved. Among them, 6 cases had LNM. Plasma from 4 individuals with no LNM was collected as a control. We extracted exosomes by ultracentrifugation, and Ex-miRNAs were profiled using small RNA next-generation sequencing followed by differential expression analysis. Based on unsupervised hierarchical clustering, the exosomal miRNAs expression profile in patients with LNMwas significantly different from the control group. Results: The results indicated that the levels of exosomal hsa-miR-1226-5p were significantly lower in the LNM group compared with nonmetastatic controls (p-value<0.05), whereas hsa-miR-145-5p, hsa-miR-1226-3p, hsa-miR-4745-5p, hsa-miR-673,5-5p, and hsa-miR-6821-5p were significantly higher in the LNM cases than in lymph node-negative group(p-value<0.05). Ex-miRNAs cargo was profiled with microarrays followed by bioinformatics analyses. Their predicted target genes involved several cancer-related pathways, including Rap1 signaling pathway, cAMP signaling pathway, Calcium signaling pathway, Hippo signaling pathway, and ECM-receptor interaction (p-value<0.05).
Conclusions: Patients with LNM represent unique plasma exosomal miRNA profiles. Some abnormally expressed Ex-miRNAs can be identified as potential biomarkers for predicting PTC LNM.