Unknown

Dataset Information

0

Proteomics-derived basal biomarker DNA-PKcs is associated with intrinsic subtype and long-term clinical outcomes in breast cancer.


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.

SUBMITTER: Asleh K 

PROVIDER: S-EPMC8429676 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7302059 | biostudies-literature
2022-05-25 | PXD029202 | Pride
| S-EPMC5955551 | biostudies-other
| S-EPMC4934839 | biostudies-other
| S-EPMC7174873 | biostudies-literature
| S-EPMC9318288 | biostudies-literature
| S-EPMC9303282 | biostudies-literature
2020-09-21 | GSE137950 | GEO
2020-04-15 | GSE137353 | GEO
| S-EPMC5310827 | biostudies-other