RESUMO
Today, we face difficulty in generating new hypotheses and understanding oral lichen planus due to the large amount of biomedical information available. In this research, we have used an integrated bioinformatics approach assimilating information from data mining, gene ontologies, protein-protein interaction and network analysis to predict candidate genes related to oral lichen planus. A detailed pathway analysis led us to propose two promising therapeutic targets: the stromal cell derived factor 1 (CXCL12) and the C-X-C type 4 chemokine receptor (CXCR4). We further validated our predictions and found that CXCR4 was upregulated in all oral lichen planus tissue samples. Our bioinformatics data cumulatively support the pathological role of chemokines and chemokine receptors in oral lichen planus. From a clinical perspective, we suggest a drug (plerixafor) and two therapeutic targets for future research.
Assuntos
Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Estudos de Associação Genética , Líquen Plano Bucal/tratamento farmacológico , Líquen Plano Bucal/genética , Terapia de Alvo Molecular , Mucosa Bucal/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Benzilaminas , Biologia Computacional , Ciclamos , Feminino , Compostos Heterocíclicos/uso terapêutico , Humanos , Masculino , Regulação para CimaRESUMO
BACKGROUND: Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to assess the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas. METHODS: Immunohistochemical expression of chemokine receptors was evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma. Clinicopathological associations were analysed using the chi-square test, survival curves were analysed according to the Kaplan-Meier method, and the Cox proportional hazard model was applied for multivariate survival analysis. RESULTS: The chemokine receptors were highly expressed in primary carcinomas, except for CCR1 and CCR3. Significant associations were detected, including the associations between CCR5 expression and lymph node metastasis (N stage, P = .03), advanced clinical stage (P = .003), poor differentiation of tumours (P = .05) and recurrence (P = .01). The high expression of CCR5 was also associated with shortened disease-free survival (HR: 2.85, 95% CI: 1.09-8.14, P = .05), but the association did not withstand the Cox multivariate survival analysis. At univariate analysis, high expression of CCR7 was associated with disease-free survival and low levels of CXCR4 were significantly associated with both disease-specific and disease-free survival. CONCLUSIONS: These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence.