Full text
| |
| Author(s): |
Mariana Bonjiorno Martins
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2015-11-12 |
| Examining board members: |
Laura Sterian Ward;
Rita de Cassia Ferreira;
Gláucia Maria Ferreira da Silva Mazeto;
Natássia Elena Búfalo;
Ligia Vera Montali da Assumpção
|
| Advisor: | Laura Sterian Ward |
| Abstract | |
Representing more than 2% of all human cancers, thyroid cancer has been increasing in many regions of the world in the recent decades. So, there has been an active sought for markers that distinguish malignancy in thyroid nodules and enable a better choice of management strategies and monitoring. Thyroid neoplastic cells are associated with a molecular profile and immune response that may be associated with malignancy and aggressiveness. The immune system has anti-inflammatory cytokines, among which are several Interleukins (ILs), that participate in the induction and effector phases of immune and inflammatory responses. This study aimed to determine whether the genes and proteins of IL-2, IL-2R, IL-4, IL-4R, IL-6, IL-6R, IL-8, IL-10 and IL-12 can be used as markers diagnosis and/or prognosis for Differentiated Thyroid Cancer (DTC). We studied a total of 300 DTC, 60 patients with benign nodules and 300 healthy controls. Genotypic analysis was performed of ILs byTaqMan® SNP Genotyping and serum dosage by ELISA. For the serum data, the IL-2 distinguished patients with active disease from without active disease (p=0.0007) benign and malignant (p<0.0001). IL-2R differentiated malignant and control groups (p<0.0001), IL-4 was the only one that did not differentiate the malignant, benign and control groups, but was greater in patients without metastasis to distance (p=0.0290) and those who higher thyroiditis (p=0.0005). The dosage of IL-6 was capable of identifying malignancies (p=0.0053); while higher levels of IL-6R were associated with the presence of active disease (p<0.0001) and metastasis diagnosis (p=0.0301), and no capsule (p=0.0310). IL-8 concentrations distinguished patients with active disease from without the active disease (p=0.0025), malignant from benign patients (p<0.0001) and the control (p=0.0016). IL-10 also proved useful in identifying malignant (p<0.0001) and multifocality (p=0.0019). And, IL-12 differentiated patients with active disease from without active disease (p<0.0001) as well as differentiate the control of malignant disease (p<0.0001). Genotype distribution of the studied polymorphisms did not correlate with the risk for DTC; did not differentiate the groups and there was no correlation with clinicopathological characteristics. As for the correlation data between the studied SNPs and serum concentrations, we observed that only SNPs IL-2 rs2069762 and IL-6R rs2228145, IL-6R rs4845622 and IL-6R rs6684439 showed influences the increased concentration of the respective ILSs. We conclude that the data in serum concentrations of IL-2, IL-2R, IL-6, IL-6R, IL-8, IL-10 and IL-12 can help in the diagnosis of malignancy and aggressiveness parameters, but cannot be used as markers for monitoring patients with DTC. As for the genes studied none of the polymorphisms are involved in pathogenicity in DTC. As for the studied polymorphisms, although none of them are involved in pathogenicity in DTC, the polymorphisms IL-2 rs2069762, IL-6R rs2228145, IL-6R rs4845622 and IL-6R rs6684439, are related to increased production of serum interleukins (AU) | |
| FAPESP's process: | 12/16830-0 - ANALYSIS OF SERUM INTERLEUKINS IL-2, IL-4, IL-4R (RECEPTOR), IL-6, IL-6R (RECEPTOR), IL-8, IL-10, IL-12 (A,B) IN THE CLINICOPATHOLOGICAL PROFILE OF DIFFERENTIATED THYROID CARCINOMA. |
| Grantee: | Mariana Bonjiorno Martins |
| Support Opportunities: | Scholarships in Brazil - Doctorate |