RESUMO
Discoidin domain receptor I (DDR1) is confirmed as a receptor tyrosine kinase (RTK), which plays a consequential role in a variety of cancers. Nevertheless, the influence of DDR1 expression and development in renal clear cell carcinoma (RCCC) are still not well corroborated. In our research, we firstly discovered that the expression level of DDR1 was remarkable related to TNM stage (p = 0.032), depth of tumor invasion (p = 0.047), and lymph node metastasis (p = 0.034) in 119 RCCC tissue samples using tissue microarray. The function of DDR1 was then evaluated in vitro using collagen I and DDR1 small interfering RNA (siRNA) to regulate the expression of DDR1 in OS-RC-2 and ACHN renal cancer cells (RCC). DDR1 expression correlated with increased RCC cell migration, invasion, and angiogenesis. Further study revealed that high expression of DDR1 can result in epithelial to mesenchymal transition (EMT) activation. Western blot assay showed that the N-cadherin protein and vimentin were induced while E-cadherin was reduced after DDR1 over expression. Our results suggest that DDR1 is both a prognostic marker for RCCC and a potential functional target for therapy.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Receptor com Domínio Discoidina 1/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Renais/patologia , Adulto , Idoso , Western Blotting , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Análise Serial de TecidosRESUMO
Purpose: Previous studies have shown that microRNA is involved in regulating a variety of human inflammatory diseases. The purpose of this study was to investigate the expression of miR-10a-3p in the blood of patients with severe pneumonia and evaluate its value in the diagnosis and prognosis of severe pneumonia. Patients and Methods: Seventy patients with severe pneumonia and 75 healthy individuals were included in this study. Venous blood of all subjects was obtained for RT-qPCR analysis to obtain the relative expression level of miR-10a-5p. The diagnostic accuracy of miR-10a-5p for severe pneumonia was assessed by ROC curve. After standardized treatment, the prognosis of patients with severe pneumonia was analyzed by a 28-day follow-up method. Kaplan-Meier curve and multivariate Cox regression analysis were used to determine the basic factors influencing the prognosis of patients. Results: Compared with healthy control, serum miR-10a-3p expression in patients with severe pneumonia was distinctly upregulated (P < 0.001). Besides, ROC analysis showed that miR-10a-3p had high diagnostic accuracy for severe pneumonia, with an AUC of 0.881, sensitivity and specificity of 75.7% and 84.0%, respectively. Kaplan-Meier curve exhibited that high miR-10a-3p expression group had a higher probability of death than those with low miR-10a-3p expression. Multivariate Cox regression analysis demonstrated that miR-10a-3p and CRP were independent risk factors affecting the prognosis of patients. Conclusion: The expression of miR-10a-3p was increased in patients with severe pneumonia, and abnormally expressed miR-10a-3p has the potential to be used as a diagnostic and prognostic marker for severe pneumonia, which provides a new biological direction for the early detection and risk assessment of severe pneumonia.