| 英文摘要 |
Immunotherapy is a treatment strategy for breast cancer, which is the most common malignancy in female patients. The role of hypoxic signaling in the progression of breast cancer has been extensively studied, but the therapeutic implication for breast cancer is not shown. This study determines effective biomarkers for hypoxic signaling for immunotherapy for breast cancer patients. Genomic, transcriptomic and immunomics data and clinical records are from The Cancer Genome Atlas (TCGA). The immunological landscape of the tumor is determined using CIBERSORT and xCell algorithms. The differential expression, predictive ability and prognostic significance of a specific biomarker for immunotherapy are substantiated using the GEO repository. The biological mechanisms for a specific biomarker in breast cancer are determined by Gene Set Enrichment Analysis (GSEA).
In terms of hypoxic biomarkers, Von Hippel-Lindau Tumor Suppressor (VHL) produces the greatest genetic alteration in breast cancer patients. Patients with VHL mRNA-high demonstrate a higher mortality rate but show no difference in terms of the microsatellite instability (MSI) score or tumor mutation burden (TMB). Breast Invasive Ductal Carcinoma (IDC) exhibits the greatest altered frequency of mRNA-High, followed by Breast Invasive Carcinoma (NOS) and Breast Invasive Lobular Carcinoma (ILC). VHL expression has a negative correlation with anti-tumoral immune cells and immunostimulators and a positive correlation with immunoinhibitors and receptors. High levels of VHL indicate a favorable response to immunotherapy. VHL expressions in breast cancer is associated with the activation of proliferation and inhibition of innate immunity. High VHL levels are also a potential biomarker for increased sensitivity to BMS4_406 and elevated resistance to cetuximab. This study shows that VHL expression is biomarker for immunosuppression, response to immunotherapy and sensitivity to BMS4_406 and cetuximab. |
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