The Significance of Transcriptomic Signatures in the Multifocal Papillary Thyroid Carcinoma: Two mRNA Expression Patterns with Distinctive Clinical Behavior from The Cancer Genome Atlas (TCGA) Database

Abstract

Background and Objectives: The association between multifocal papillary thyroid carcinoma (PTC) and tumor aggressiveness remains controversial. The aim of study is to evaluate molecular subtypes of multifocal PTCs using multiplatform genomic analysis. Materials and Methods: Statistical analysis and genomic analysis were performed for gene expression data and clinical data of multifocal PTCs in The Cancer Genome Atlas data. Clinicopathologic findings, recurrence-free survival (RFS), copy number alteration and somatic mutation status in patients in relation to molecular subtypes were analyzed. Results: Multiplatform genomic analysis revealed that multifocal PTCs (n=226) were divided into two distinct molecular subgroups. Participants in cluster 2 showed significantly increased risk of extrathyroidal extension, lymph node metastasis, and BRAFV600E mutation compared to patients in cluster 1. To exclude the effect of BRAF mutation and RAS mutation on tumor aggressiveness, we compared clinical parameters between two clusters in patients without BRAF or RAS mutation. Cluster 2 showed significantly higher risk of lymph node metastasis compared to cluster 1. Conclusion: Multifocal PTC has two distinct molecular subtypes with distinctive clinical behaviors. Our data suggested the clinical implications of the transcriptomic signature to predict clinical outcomes of multifocal PTC.