RESUMO
The detection of genes related to the lifetime of patients with clear cell renal cancer provides information on the mechanisms of the tumor development and can be the basis for creating approaches to predict patient survival. In this paper, the expression of genes regulated by the HIF2α transcriptional factor was studied. Based on the results obtained here and previously identified genes regulated by the transcriptional factor HIF1α, a new panel of 6 genes, including the BAP1 gene, was proposed. Expression of genes of this panel allows predicting the survival of patients with clear cell renal cancer with high sensitivity (93%), specificity (96%), and relative risk (21.5). After verification, the application of this panel can be useful for personalized treatment of patients with clear cell renal cancer, which will increase the effectiveness of therapy.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma de Células Renais/patologia , Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Renais/patologiaRESUMO
An association was found between reduced expression of miR-34a, miR-146a with both metastasis to regional lymph nodes (relative risk RR=10.50 and RR=5.25, respectively) and the development of distant metastases (RR=9.50 and RR=4, 40, respectively) in gastric cancer. They are excellent classifiers: AUC>0.9 for both miRNAs. The association of miR-335 expression with metastasis to the lymph nodes is much weaker, but it is also a good classifier for identifying a group with distant metastasis (RR=5.90). A correlation was found between the expression of miR-34a and miR-146a during metastasis, which is absent in non-metastatic tumors. Thus, miR-34a, miR-146a, and miR-335 miRNAs can be proposed as candidates for biomarkers of the risk of gastric cancer metastasis.
Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , TranscriptomaRESUMO
We analyzed association of the levels of VEGFA, RAF1, and mTOR gene expression in the tissue of clear-cell renal cell carcinoma (ccRCC) with tumor metastasizing. Significant association with metastases was found only for VEGFA gene: OR=6.641, 95%CI=2.111-20.696. The risk of metastasis associated with reduced expression of VEGFA gene - 2.467, 95%CI=1.238-4.915. An association of VEGFA gene expression with the time to the metastasis appearance was revealed (p=0.0005). Reduced expression of the VEGFA gene is associated with reduction of the time to metastasis appearance; the median of this time is shifted from 46 to 2 months. Analysis of tumor samples with reduced expression of the VEGFA gene revealed association of increased expression of RAF1 (p=0.003) and mTOR genes (p=0.038) with metastasis.
Assuntos
Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Proteínas Proto-Oncogênicas c-raf/genética , Serina-Treonina Quinases TOR/genética , Fator A de Crescimento do Endotélio Vascular/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-raf/metabolismo , Curva ROC , Risco , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The main mechanisms of pathogenesis of clear cell renal cell carcinoma (CCRCC) are realized through the PI3K-AKT-mTOR and Ras-RAF-ERK signaling pathways. Targeted therapy is directed primarily at the genes and their encoded products that are components of these pathways. The levels of expression and coexpression of target genes were determined, and the difference in the functioning of the genes of one of the two major signaling pathways in tumors of CCRCC patients with different life duration (more and less than 3.5 years) and the relationship of the VEGFA gene expression level with the life duration was revealed.
