A high incidence of lymph node metastasis has been described in papillary thyroid carcinoma (PTC), which is related to an increased risk of tumor recurrence. Biomarkers have potential to be used as predictive tool to identify patients with high risk to recur in comparison with imaging tests, which present low sensitivity to detect lymph node metastasis. The aim of this study is to identify molecular markers able to predict lymph node metastasis in PTC patients.
Messenger RNA sequencing data obtained from TCGA (Illumina HiSeq level 3) of PTC were used in a preliminary screening. From 507 patients, 200 were filtered to avoid confounding factors. Cases presenting lymph nodes (LN) positive (N1 = 107) had pathological confirmation of LN metastasis at diagnosis with unicentric primary tumor. Cases LN negative (N0 = 93) had pathological confirmation of LN disease-free; they were no submitted to ablation by radioiodine therapy neither presented loco-regional recurrence after 1-year of follow-up. Differentially expressed genes were submitted to in silico pathway analysis using the Reactome tool. Selected transcripts were further assessed by RT-qPCR using Taqman assays (Applied Biosystems) to confirm the findings in an independent set of 72 PTC samples.
Based on TCGA database, 334 transcripts were detected by comparing N1 versus N0 tumors (random variance t test FDR 2). Pathway analysis revealed an enrichment of genes related to collagen degradation and formation, degradation of the extracellular matrix and activation of matrix metalloproteinases (FDR
This study revealed a potential involvement of extracellular matrix remodeling pathways in the LN metastasis in PTC. In addition, AREG, S100A2, S100A10, SCEL, PDLIM4 and DIO2 genes are promising markers to discriminate PTC tumors with higher risk of presenting cervical LN metastasis at diagnosis.
Clinical trial identification
Legal entity responsible for the study
AC Camargo Cancer Center
All authors have declared no conflicts of interest.