Int J Thyroidol.  2020 May;13(1):1-12. 10.11106/ijt.2020.13.1.1.

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

• Kang YE
• Hwang B
• Lee JH
• Shong M
• Yi HS
• Koo BS
• Lee DJ

• KMID: 2502254
• DOI: http://doi.org/10.11106/ijt.2020.13.1.1

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.

Keyword

Thyroid neoplasm; Gene expression profiling; Genomics

Figure

• 

  Fig. 1 Unsupervised clustering of multifocal papillary thyroid carcinomas (PTCs) revealing two distinct molecular subtypes. A hierarchical clustering of gene expression data from 226 multifocal PTC cases in The Cancer Genome Atlas (TCGA) data. Gene expression levels that were at least 2-fold different in at least 50 cases relative to the median value across cases were selected for hierarchical clustering analysis (3134 gene features). Data are given in matrix format, in which rows represent individual genes and columns represent each patient. Each cell in the matrix represents expression level of a gene feature in an individual pattern. Red and green colors in cell indicate relative high and low expression, respectively, as indicated in the scale bar.

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  Fig. 2 Copy number (CPN) alteration according to each cluster. The amount of CPN variation of PTC is small (−0.2 to +0.1) when compared to other cancer type. Multifocal PTCs in cluster 1 showed frequent CPN alteration when compared to cluster 2.

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  Fig. 3 Each cluster-specific gene expression patterns shown in heatmap. Data given in the matrix represent the expression level of a gene feature in an individual patient. We selected 100 group-specific genes to draw the heatmap. Red and green colors in cell indicate relative high and low expression, respectively.

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