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Publications

Journal Article Ppublish

PubMed: 40669608 DOI: 10.1016/j.mce.2025.112614

Association between BRAFV600E mutation and gene expression of CLDN1, TIMP1, and KRT19 in papillary thyroid cancer.

Mol Cell Endocrinol 607:112614

Authors: Andrea Ross-Orozco, Anette Roxana Gastelum-Quiroz, Marco Alvarez-Arrazola, Fred Luque-Ortega, Alejandra Martínez-Camberos, Karla Morales-Hernandez, F Lopez-Herrera Y Cairo, Noemí García-Magallanes

Affiliations

  • Laboratorio de Biomedicina y Biología Molecular, Ingeniería en Biotecnología, Universidad Politécnica de Sinaloa, Mazatlán, 82199, Mexico; Posgrado en Ciencias Biomédicas, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, 80010, Mexico.
  • Laboratorio de Biomedicina y Biología Molecular, Ingeniería en Biotecnología, Universidad Politécnica de Sinaloa, Mazatlán, 82199, Mexico; Alvarez & Arrazola Radiólogos, Mazatlán, 82140, Mexico.
  • Laboratorio de Ciencias Básicas, Facultad de Odontología, Universidad Autónoma de Sinaloa, Culiacán, 80013, Mexico.
  • Licenciatura en Ciencias Biomédicas, Universidad Autónoma de Occidente, Mazatlán, 82100, Mexico.
  • Posgrado en Ciencias Biomédicas, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, 80010, Mexico; Licenciatura en Ciencias Biomédicas, Universidad Autónoma de Occidente, Mazatlán, 82100, Mexico.
  • Laboratorio de Biomedicina y Biología Molecular, Ingeniería en Biotecnología, Universidad Politécnica de Sinaloa, Mazatlán, 82199, Mexico.
  • Laboratorio de Biomedicina y Biología Molecular, Ingeniería en Biotecnología, Universidad Politécnica de Sinaloa, Mazatlán, 82199, Mexico.

Abstract

The molecular mechanisms driving Papillary Thyroid Cancer (PTC) progression remain incompletely understood, although mutations in BRAF, are believed to affect the expression of key markers involved in PTC development. This study aimed to investigate the BRAFV600E mutation and its association with the expression of CLDN1, TIMP1, and KRT19 in PTC. A total of 93 thyroid samples were retrospectively analyzed: 42 cytologically diagnosed as PTC (Bethesda VI/V), 4 suspicious for malignancy (Bethesda V), and 47 as nodular hyperplasia (Bethesda II). The presence of the BRAFV600E mutation and the expression levels of CLDN1, TIMP1, and KRT19 were determined using qPCR. BRAFV600E genotypes included 70.2 % TT (wild-type), 17 % TA (heterozygous), and 12.8 % AA (mutant homozygous), with a mutated allele frequency of 0.210. The TA genotype was exclusive to the cancer group and significantly increased malignancy risk (OR 3.667; 95 % CI 2.473-5.437; p < 0.001). Patients harboring the mutated A allele were significantly younger (p = 0.029) and exhibited higher expression of all three genes. Using Youden-derived cutoffs from ROC analysis, TIMP1 overexpression (cutoff 1.148) was most strongly associated with BRAFV600E (OR 4.34; 95 % CI 1.82-10.33; p < 0.001). The BRAFV600E mutation and TIMP1 overexpression are strongly associated with malignant thyroid nodules, suggesting a role in the molecular pathogenesis of PTC.

MeSH

Thyroid Cancer, Papillary, Genes, Thyroid Nodule, Neoplasms, Thyroid Gland, Hormones, Alleles, Genotype, Thyroid Neoplasms, Mutation, Gene Expression