Clinical utility of and its receptors ( and ) in thyroid nodules: evaluation based on single nucleotide polymorphisms and mRNA analysis.
Karina Colombera Peres, Larissa Teodoro, Laís Helena Pereira Amaral, Elisângela Souza Teixeira, Icléia Siqueira Barreto, Leandro Luiz Lopes de Freitas, Valdemar Maximo, Lígia V Montalli Assumpção, Natassia Elena Bufalo, Laura Sterian Ward
Author Information
Karina Colombera Peres: Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil, karinacolombera@gmail.com.
Larissa Teodoro: Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Laís Helena Pereira Amaral: Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Elisângela Souza Teixeira: Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Icléia Siqueira Barreto: Departamento de Anatomia Patológica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Leandro Luiz Lopes de Freitas: Departamento de Anatomia Patológica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Valdemar Maximo: Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
Lígia V Montalli Assumpção: Divisão de Endocrinologia, Departamento de Medicina, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Natassia Elena Bufalo: Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Laura Sterian Ward: Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
OBJECTIVE: Abnormalities involving the gene and its receptors are common in several types of cancer and often related to tumor progression. We investigated the role of single nucleotide polymorphisms (SNP) in the susceptibility to cancer, their impact on its features, as well as the role of mRNA expression of these genes in thyroid malignancy. METHODS: We genotyped , , and SNPs in 157 papillary thyroid cancer (PTC) patients and 200 healthy controls. Further, we investigated RNA samples of 47 PTC and 80 benign nodules, searching for differential mRNA expression. RESULTS: SNPs rs1800472 and rs1800469 were associated with characteristics of PTC aggressiveness. Effect predictor software analysis of nonsynonymous SNP rs1800472 indicated increasing protein stability and post-translational changes. mRNA expression was upregulated in PTC and downregulated in benign samples, differentiating malignant from benign nodules (p<0.0001); PTC from goiter (p<0.0001); and PTC from FA (p<0.0001). mRNA expression was upregulated in goiter and PTC, but downregulated in FA, distinguishing PTC from goiter (p=0.0049); PTC from FA (p<0.0001); and goiter from FA (p=0.0267). On the other hand, was downregulated in all histological types analyzed and was not able to differentiate thyroid nodules. CONCLUSION: polymorphism rs1800472 may confer greater activity to TGF-β1 in the tumor microenvironment, favoring PTC aggressiveness. Evaluation of and mRNA levels may be useful to identify malignancy in thyroid nodules.
