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Human epidermal growth factor receptor 2-positive (HER2+) breast cancer, which accounts for 15-20% of all breast cancer, is associated with tumor recurrence and poor prognosis. RAS association domain family protein 1 subtype A (RASSF1A) is a tumor suppressor that is silenced in a variety of human cancers. The present study aimed to investigate the role of RASSF1A in HER2+ breast cancer and the therapeutic potential of RASSF1A-based targeted gene therapy for this malignancy. RASSF1A expression in human HER2+ breast cancer tissues and cell lines was evaluated by reverse transcription PCR and western blot analysis. The associations between tumorous RASSF1A level and tumor grade, TNM stage, tumor size, lymph node metastasis and five-year survival were examined. HER2+ and HER2-negative (HER2-) breast cancer cells were transfected with a lentiviral vector (LV-5HH-RASSF1A) that could express RASSF1A under the control of five copies of the hypoxia-responsive element (5HRE) and one copy of the HER2 promoter (HER2p). Cell proliferation was evaluated by the MTT and colony formation assays. It was found that tumorous RASSF1A level was negatively associated with tumor grade (P=0.014), TNM stage (P=0.0056), tumor size (P=0.014) and lymph node metastasis (P=0.029) and positively associated with five-year survival (P=0.038) in HER2+ breast cancer patients. Lentiviral transfection of HER2+ breast cancer cells resulted in increased RASSF1A expression and decreased cell proliferation, especially under hypoxic conditions. However, lentiviral transfection of HER2-breast cancer cells did not affect RASSF1A expression. In conclusion, these findings verified the clinical significance of RASSF1A as a tumor suppressor in HER2+ breast cancer and supported LV-5HH-RASSF1A as a potential targeted gene therapy for this malignancy.

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Background:With low response to present immunotherapy, it is imperative to identify new immune-related biomarkers for more effective immunotherapies for oral cancer.Methods:RNA profile for 390 oral cancer patients and 32 normal samples were downloaded from the Cancer Genome Atlas (TCGA) database and differentially expressed genes (DEGs) were analyzed. Immune genesets from Immportrepository were overlapped with DEGs. After implementing univariate Cox analysisand the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, key immune-related gene pairs (IRGPs) among the overlappedDEGs for predicting the survival riskwere obtained. Then, the cutoff of risk score was calculated by receiver operating characteristic (ROC) curve to stratify oral cancer patients into high and low-risk groups. Multivariate Cox analysis was used to analyze independent prognostic indicator fororal cancer.Besides, infiltration of immune cells, functional annotation and mutation analysis of IRGPs were conducted.Biological function correlated with IRGPs were enriched by Gene Set Enrichment Analysis (GSEA) method. Results: We identified698 differentially expressed genes (DEGs)in response to oral cancer. 17IRGPs among the DEGs were identified and integrated into a risk score model. Patients in high-risk group have significantly worse prognosis than those in low-risk group. Meanwhile, IRGPs model was identified as an independent prognostic factor for oral cancer. Different infiltration pattern of immune cells were found between high- and low-risk groups that more types of T and B cells were enriched in low-risk group. More immune-related signaling pathways were highly enriched in low-risk group. And Tenascin C (TNC) was the most frequently mutated genes. We have developed a novel 17-IRGPs signature for risk stratification and prognostic predication of oral cancer.Conclusion: Our study provides a foundation for improved immunotherapy and prognosis and is beneficial to the individualized management of oral cancer patients.