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BRAF mutation, selected miRNAs and genes expression in primary papillary thyroid carcinomas and local lymph node metastases

D. Kalfert, M. Ludvikova, M. Pesta, T. Hakala, L. Dostalova, H. Grundmannova, J. Windrichova, K. Houfkova, T. Knizkova, J. Ludvik, J. Polivka, I. Kholova

. 2024 ; 258 (-) : 155319. [pub] 20240423

Language English Country Germany

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24013655

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.

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$a Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.
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$a Ludvikova, Marie $u Department of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen 32300, Czech Republic. Electronic address: ludvikova.m@email.cz
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$a Pesta, Martin $u Department of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen 32300, Czech Republic
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$a Hakala, Tommi $u The Wellbeing Services County of Pirkanmaa, Department of Surgery, Tampere University Hospital, Tampere, Finland
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$a Dostalova, Lucie $u Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Motol, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Grundmannova, Hana $u Laboratory of Immunoanalysis, University Hospital in Pilsen, Pilsen, Czech Republic
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$a Knizkova, Tereza $u Department of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen 32300, Czech Republic
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$a Polivka, Jiri $u Department of Histology and Embryology and Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
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$a Kholova, Ivana $u Pathology, Fimlab Laboratories, Tampere, Finland and Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland
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