Study of TGF-ß1 in the differentiated thyroid carcinoma

Author(s)

Karina Colombera Peres

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2018-01-12

Examining board members

Laura Sterian Ward; Murilo Vieira Geraldo; Gláucia Maria Ferreira da Silva Mazeto

• Advisor: Laura Sterian Ward; Natássia Elena Búfalo

Abstract

Thyroid nodules are often identified in clinical practice, presenting a higher increase in the last decades. Despite the high accuracy, the diagnosis of DTC through FNAC analysis shows deficiencies: 15-20% of samples submitted to cytological analysis are classified as unsatisfactory/non-diagnostic samples or lesions of undetermined significance, leading the patient to a thyroidectomy to clarify the diagnosis. The transforming growth factor-ß (TGF-ß) is a multifunctional cytokine acting on different characteristics and biological functions and on the regulation of the immune system. Its signaling occurs through two transmembrane receptors: type I receptor (TßRI) and type II receptor (TßRII). Several studies have reported a disturbance or loss of TGF-ß1 signaling and its receptors in cancer, as well polymorphisms in these genes are investigated and associated with several pathologies. The aim of this work is to investigate the utility of TGFB1, TGFBR1 and TGFBR2 genes as diagnostic and/or prognostic markers in patients with thyroid nodules, pursuing to correlate these results with clinical-pathological characteristics. For investigation of TGFB1 (rs1800469, rs1800472, rs11466321, rs2241716, rs8110090), TGFBR1 (rs10512263, rs7850895) and TGFBR2 polymorphisms (rs2228048) we investigated 339 patients with malignant and benign thyroid nodules by Taqman SNP Genotyping technique and 141 normal, malignant and benign tissue samples were evaluated for the mRNA expression of the same genes above by qPCR. Two polymorphisms, rs1800469 and rs1800472, of the TGFB1 gene demonstrated a correlation of the polymorphic genotype with tumor aggressiveness characteristics such as absence of capsule and absence of lymph node metastasis at diagnosis, respectively. The rs10512263 polymorphism of the TGFBR1 gene demonstrated association of the polymorphic genotype with absence of invasion. The gene expression of TGFB1 was increased in malignant tissues, as well as TGFBR1, but not TGFBR2. In conclusion, our data demonstrate that TGFB1 gene expression may be a useful tool to aid diagnosis of benign thyroid nodules and polymorphisms of the TGFB1 and its TGFBR1 receptor, but not TGFBR2, may help in the prognosis of DTC patients (AU)

• FAPESP's process: 15/19117-0 - Study of TGF-²1 in differentiated thyroid carcinoma
• Grantee: Karina Colombera Peres
• Support Opportunities: Scholarships in Brazil - Master