ABSTRACT
BACKGROUND: We evaluated microRNAs and extracellular matrix component profiles in squamous cell carcinoma of the oral cavity (OSCC) in comparison to healthy mucosa. METHODS: Retrospective study investigating 64 microRNAs related to oncogenic process and to constituents of the extracellular matrix. We also performed immunohistochemical assays for molecules involved in the same biological processes. RESULTS: High expression of miR-21-5p (p < 0.001) and miR-106-5p (p < 0.001) and low expression of miR-320a (p = 0.001) and miR-222-3p (p = 0.001) were predictors of malignancy. Individually, miR-21-5p exhibited the best statistical performance (area under the curve = 0.972; 95% confidence interval: 0.911-1.000) in the differentiation between tumor tissue and healthy mucosa. Moreover, tumor sample showed increased expression of MMP-2, MMP-9, α-laminin, and ß-laminin in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane. CONCLUSION: The present study demonstrates the biological effects of microRNAs on the carcinogenesis of OSCC as well as the intense modification of the tumor microenvironment.
Subject(s)
Carcinoma, Squamous Cell , MicroRNAs , Mouth Neoplasms , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation , Extracellular Matrix/genetics , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Mouth Neoplasms/genetics , Retrospective Studies , Tumor Microenvironment/geneticsABSTRACT
The objective of the present study was to evaluate the role of microRNA-mediated remodeling of the extracellular matrix in the process of tumor invasion of oral squamous cell carcinoma and to evaluate its relationship with the prognosis of these patients. This was a retrospective study on material from the paraffin blocks of patients operated on for oral squamous cell carcinoma, in addition to a group of healthy oral mucosa samples of paired patients. miR-1-3p, miR-133-3p, and miR-21-5p were differentially expressed between the superficial and deep tumor groups. miR-21-5p was the one with the greatest accuracy in the differentiation between superficial and deep tumors. By immunohistochemistry, the group of deep tumors showed greater immunoreactivity to matrix metalloproteinases 2 and 9 and laminin α in tumor-associated fibroblasts, with consequent degradation of the basal membrane, measured by greater loss of continuity of type IV collagen. This process was also associated with lower and higher expression of miR-1-3p and miR-21-5p, respectively. There was also a trend toward better overall and disease-free survival rates in patients with higher miR-133a-3p. The present study showed the interaction between microRNAs and extracellular matrix remodeling in oral squamous cell carcinoma.
Subject(s)
Cancer-Associated Fibroblasts/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Adult , Aged , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Combined Modality Therapy , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Middle Aged , Mouth Neoplasms/diagnosis , Mouth Neoplasms/therapy , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , RNA Interference , ROC CurveABSTRACT
Este trabalho tem como objetivo revisar a literatura médica enfocando os fatores de risco relacionados à transmissão vertical do vírus da hepatite C. Dentre estes fatores estão a carga viral do vírus da hepatite C (HCV) na gestante, a co-infecção HIV/HCV, a via de parto adotada, o uso de drogas intravenosas durante a gestação e o aleitamento materno. Os estudos analisados apresentaram uma taxa de transmissão vertical que variou entre 2,3 e 13 porcento, demonstrando que as altas cargas virais de HCV no sangue materno e a co-infecção HIV/HCV estão diretamente relacionadas ao aumento dessa taxa. Dados conflitantes foram obtidos quanto ao uso de drogas intravenosas durante a gestação e a elevação da taxa de transmissão vertical do HCV. No que diz respeito à via de parto adotada e à prática do aleitamento materno não houve dados que pudessem demonstrar relação com um maior risco de transmissão vertical.
