BRAF-positive multifocal and unifocal papillary thyroid cancer show different messenger RNA expressions

Abstract

Objective Thyroid cancer is the most common malignant endocrine tumour, and its incidence has continuously increased worldwide over the past three decades. We focused on the association of multifocal papillary thyroid carcinoma (PTC) with messenger RNA (mRNA) expression to characterize how molecular and histopathologic features relate to multifocality. Design A retrospective cohort study. Patients The primary and processed data were downloaded from The Cancer Genome Atlas. A total of 490 patients were included in this study. Methods The statistical significance of differences in sex, age, histology, LN metastasis and recurrence were analysed using chi-squared test. To identify differentially expressed genes between BRAF (+) multifocal and unifocal PTCs and between BRAF (-) multifocal and unifocal PTCs, we used the Significance Analysis of Microarray. Over-representation analysis is conducted using CPDB. Results A total of 237 patients had BRAF (+) PTCs, whereas 253 had BRAF (-) PTCs. There were 110 patients with multifocal PTCs and 127 with unifocal PTCs in the BRAF (+) group and 116 patients with multifocal PTCs and 137 with unifocal PTCs in the BRAF (-) group. In BRAF (+) group, multifocal PTCs had increased expression of 158 mRNAs as compared to that in unifocal PTCs. Ten mRNAs were involved in Wnt-related pathways, and seven mRNAs were included in pluripotency-related pathways. Conclusion Multifocal PTCs have higher expression of mRNAs in Wnt- and pluripotency-related pathways when BRAF mutation is present. This might be the mechanism that accounts for the difference between multifocal and unifocal PTCs.