A miRNA-clinicopathological nomogram for the prediction of central lymph node metastasis in papillary thyroid carcinoma-analysis from TCGA database

It is of significance to evaluate central lymph node status in patients with papillary thyroid carcinoma (PTC), because it can decrease postoperative complications resulting from unnecessary prophylactic central lymph node dissection (CLND). Due to the low sensitivity and specificity of neck ultrasonography in the evaluation of central lymph node metastasis (CLNM), it is urgently required to find alternative biomarkers to predict CLNM in PTC patients, which is the main purpose of this study. RNA-sequencing datasets and clinical data of 506 patients with thyroid carcinoma from the Cancer Genome Atlas (TCGA) database were downloaded and analyzed to identify differentially expressed miRNAs (DEMs), which can independently predict CLNM in PTC. A nomogram predictive of CLNM was developed based on clinical characteristics and the identified miRNAs. Receiver operating characteristics curves were drawn to evaluate the predictive performance of the nomogram. Bioinformatics analyses, including target genes identification, functional enrichment analysis, and protein–protein interaction network, were performed to explore the potential roles of the identified DEMs related to CLNM in PTC. A total of 316 PTC patients were included to identify DEMs. Two hundred thirty-seven (75%) PTC patients were randomly selected from the 316 patients as a training set, while the remaining 79 (25%) patients were regarded as a testing set for validation. Two DEMs, miRNA-146b-3p (HR: 1.327, 95% CI = 1.135–1.551, P = .000) and miRNA-363–3p (HR: 0.714, 95% CI = 0.528–0.966, P = .029), were significantly associated with CLNM. A risk score based on these 2 DEMs and calculating from multivariate logistic regression analysis, was significantly lower in N0 group over N1a group in both training (N0 vs N1a: 2.04 ± 1.01 vs 2.73 ± 0.61, P = .000) and testing (N0 vs N1a: 2.20 ± 0.93 vs 2.79 ± 0.68, P = .003) sets. The nomogram including risk score, age, and extrathyroidal extension (ETE) was constructed in the training set and was then validated in the testing set, which showed better prediction value than the other three predictors (risk score, age, and ETE) in terms of CLNM identification. Bioinformatics analyses revealed that 5 hub genes, SLC6A1, SYT1, COL19A1, RIMS2, and COL1A2, might involve in pathways including extracellular matrix organization, ion transmembrane transporter activity, axon guidance, and ABC transporters. On the basis of this study, the nomogram including risk score, age, and ETE showed good prediction of CLNM in PTC, which has a potential to facilitate individualized decision for surgical plans.