Detalhes bibliográficos
| Ano de defesa: |
2016 |
| Autor(a) principal: |
Graciele Domitila, Tenani
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| Orientador(a): |
Dorotéia Rossi Silva, Souza
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| Banca de defesa: |
William José, Duca,
Ana Elizabete, Silva |
| Tipo de documento: |
Dissertação
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| Tipo de acesso: |
Acesso aberto |
| Idioma: |
por |
| Instituição de defesa: |
Faculdade de Medicina de São José do Rio Preto
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| Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências da Saúde::-6954410853678806574::500
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| Departamento: |
Faculdade 1::Departamento 1::306626487509624506::500
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| País: |
Brasil
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| Palavras-chave em Português: |
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| Palavras-chave em Inglês: |
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| Área do conhecimento CNPq: |
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| Link de acesso: |
http://bdtd.famerp.br/handle/tede/407
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Resumo: |
Background - Hepatocellular carcinoma (HCC) is highlighted as the most aggressive malignant liver tumor. The identification of candidate genes to become biomarkers may help to clarify the pathophysiology of HCC, as well as the diagnosis of the disease at early stage, leading to new therapeutic interventions. Objectives -To evaluate the association of genetic variants and the gene expression involved in the cell signaling process, apoptosis, and angiogenesis with HCC, to characterize risk subgroups and identify biological markers for early diagnosis, prognosis and treatment of the disease. Casuistics and Methods – We studied 343 subjects, 102 with HCC (SG = study group) and 215 controls (CG = control group) for the analysis of PTEN polymorphisms (rs10490920, rs532678 and rs701848) and VEGF-A (rs3025039 and rs1570360). For gene expression analysis of PTEN and PIK3CA, 24 patients with HCC were selected (SGge = Study Group of gene expression), 16 with cirrhosis (CiGge = Cirrhosis Group of gene expression) and 10 controls who underwent bileo and digestive surgery (CGge = Group control of gene expression). The polymorphisms of related genes were analyzed by PCR/RFLP (polymerase chain reaction/restriction fragments length polymorphism), while the gene expression (fresh liver tissue) by qPCR (quantitative/polymerase chain reaction). Data from the clinical profile, lifestyle and comorbidities were obtained from medical records and questionnaire. Alpha error level was set at 5%. Results - Male gender, advanced age, smoking, alcohol consumption and diabetes mellitus (DM) prevailed in the group with HCC compared to the control (P<0.05). Genetic polymorphisms: PTEN- rs10490920 - The T/T genotype was noted in both groups followed by T/C, and the T allele (P>0.05). PTEN- rs532678- The genotype T/C was the most common in both groups, followed by C/C, and the C allele was predominant in GE compared to control group (P>0.05). PTEN- rs701848- The genotype C/C was highlighted in SG compared to CG, followed by T/T, and the T allele (P>0.05). VEGF-A- rs3025039- The C/C genotype is distinguished in both groups (P>0.05), the same occured for the C allele (P = 0.4226). VEGF-A- rs1570360 – G/G genotype prevailed in both groups (P>0.05), as well as the G allele (P=0.6387). Although similarity between the groups for genotypic and allelic distribution was observed, mutant PTEN and VEGF-A alleles prevailed in patients with HCC and tobacco and alcohol consumption, compared to the control group (P <0.05). PTEN and VEGF haplotype analysis was similar among the groups (P>0.05). Gene expression - PTEN expression levels was decreased in patients with HCC (median= 0,908) compared to cirrhotic patients (median = 5.93, P=0.0347). PIK3CA expression levels (median- HCC= 0,108; cirrhosis= 0,493) were similar between groups (P> 0.05). Conclusion – PTEN and VEGF-A genetic variants, as well as their haplotypes were not associated to HCC. Reduced gene expression of PTEN in tumor tissue can be associated with HCC, while PIK3CA does not differentiate between patients with HCC from those with cirrhosis. It stands out as independent risk factors for HCC, smoking, alcohol consumption, male sex, advanced age and DM. PTEN and VEGF-A mutant alleles, particularly in the presence of smoking and alcohol consumption may enhance the risk for HCC. |
