Abstract
Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A—U133, set B—HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: IGFBP3, (most significant) and ECM1. However, when analyzed on an independent dataset by qPCR, the IGFBP3 gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.
Highlights
Thyroid cancer incidence has increased in recent years
Multigene expression signatures were characterized for different neoplasms, aiming to derive clinically meaningful classifiers
The first group of 15 papillary thyroid carcinoma (PTC) patients who developed distant metastases was compared to 56 M0 patients
Summary
Thyroid cancer incidence has increased in recent years. The estimated morbidity is 15.8 persons per 100,000 population (8.0 per 100,000 men and 23.3 per 100,000 women), which represents 3.0% of all new cancer cases diagnosed in the United States [1]. Better availability of sonography leads to the detection of small lesions, which are mostly clinically asymptomatic [2]. The most common type—papillary thyroid carcinoma (PTC)—constitutes 65%−93% of all thyroid cancer cases, depending on the analyzed population [3]. Five-year overall survival for thyroid cancer is 98.2% [1]. Despite the increased number of new cases, the number of deaths remains stable, and it is 0.5 per 100,000 population
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