| Autor: |
Karama Asleh, Nazia Riaz, Angela S. Cheng, Dongxia Gao, Samuel C. Y. Leung, Meenakshi Anurag, Torsten O. Nielsen |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
npj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2374-4677 |
| DOI: |
10.1038/s41523-021-00320-x |
| Popis: |
Abstract Precise biomarkers are needed to guide better diagnostics and therapeutics for basal-like breast cancer, for which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has been recently reported by the Clinical Proteomic Tumor Analysis Consortium as the most specific biomarker. We evaluated DNA-PKcs expression in clinically-annotated breast cancer tissue microarrays and correlated results with immune biomarkers (training set: n = 300; validation set: n = 2401). Following a pre-specified study design per REMARK criteria, we found that high expression of DNA-PKcs was significantly associated with stromal and CD8 + tumor infiltrating lymphocytes. Within the basal-like subtype, tumors with low DNA-PKcs and high tumor-infiltrating lymphocytes displayed the most favourable survival. DNA-PKcs expression by immunohistochemistry identified estrogen receptor-positive cases with a basal-like gene expression subtype. Non-silent mutations in PRKDC were significantly associated with poor outcomes. Integrating DNA-PKcs expression with validated immune biomarkers could guide patient selection for DNA-PKcs targeting strategies, DNA-damaging agents, and their combination with an immune-checkpoint blockade. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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