RESUMO
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer in adults. Our aim is to evaluate genes and miRNAs expression profiles involved with angiogenesis and tumor characteristics in ccRCC. METHODS: The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b; 29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-α, VHL, PDGF, VEGF, VEGFR1 and VEGFR2 were analyzed using qRT-PCR in tumor tissue samples from 56 patients with ccRCC. Five samples of benign renal tissue were utilized as control. The expression levels of miRNAs and genes were related to tumor size, Fuhrman nuclear grade and microvascular invasion. RESULTS: miR99a was overexpressed in most samples and its target gene mTOR was underexpressed, this also occurs for miRNAs 106a, 106b, and their target gene VHL. An increase in miR-200b was correlated with high-risk tumors (p = 0.01) while miR-126 overexpression was associated with Fuhrman's low grade (p = 0.03). CONCLUSIONS: Our results show that in ccRCC there are changes in miRNAs expression affecting gene expression that could be important in determining the aggressiveness of this lethal neoplasia.
Assuntos
Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Renais/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Carcinoma de Células Renais/metabolismo , Feminino , Humanos , Neoplasias Renais/metabolismo , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismoRESUMO
BACKGROUND: PD-L1 is a glycoprotein from the family of T-cell co-stimulatory molecules that are constitutively expressed by macrophages. Aberrant expression of PD-L1 is observed in human cancers associated with inhibition of the tumor-directed T-cell immune response. There are few reports in the literature evaluating PD-L1 expression in association to prognosis specifically in renal cell cancer clear cell type (RCC-CC). METHODS: Immunohistochemistry using a PD-L1 polyclonal antibody was performed on a tissue microarray (TMA) that contained 115 surgical specimens of RCC-CC. Cases were classified based on the absence or presence of staining intensity in the cytoplasm and membranes of the tumor cells. Statistical analysis was used to determine the association of PD-L1 expression with classic prognostic factors and tumor recurrence. RESULTS: PD-L1 expression was positive in 56.5 % of tumors. The univariate analysis showed a correlation between PD-L1 expression and nuclear Fuhrman grade (p = 0.021) and microvascular tumor embolization (p = 0.039). One hundred and four patients were monitored for a mean time of 115.7 months. Seventeen patients (16.3 %) suffered tumor recurrence. Negative outcomes were associated with higher nuclear grade tumors, PD-L1 expression, and the presence of microvascular invasion. CONCLUSION: Our findings confirm that PD-L1 expression is an important prognostic factor in RCC-CC.