Home Blog of Signal Transduction Metabolism OXPHOS High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer

Background: Mutations of BRCA genes are the most studied in breast cancer, but the clinical relevance of BRCA2 gene expression has been less well studied. Given that BRCA2 is a DNA repair gene, we hypothesized that high BRCA2 expression is associated with highly proliferative and aggressive biology in breast cancer.

Materials and methods: A total of 4342 breast cancer patients were analyzed from The Cancer Genome Atlas (TCGA, n = 1069) as the testing cohort and Gene Expression Omnibus (GEO) dataset GSE96058 (n = 3273) as a validation cohort.

Results: There was no relationship between BRCA2 mutation and BRCA2 gene expression. BRCA2 high expression breast cancer was associated with higher Nottingham grade (p < 0.001), with high proliferation (MKI-67, p < 0.001), and with higher intratumor heterogeneity, homologous recombination deficiency, mutation rate, fraction altered, and neoantigens (all p < 0.001). BRCA2 high expression was associated with E2F1, RB1, PALB2, and PARP, as well as cell proliferation-related gene sets, E2F targets, G2M checkpoints, and mitotic spindle, and with less ESR1 and ER response early and late gene sets. They were associated with significantly reduced number of stroma cells and with high infiltration of both favorable and unfavorable immune cells. BRCA2 high expression significantly correlated with response to olaparib, a PARP inhibitor, and inversely with cyclophosphamide in ER-positive/HER2-negative tumors, but not in TNBC.

Conclusions: BRCA2 high gene expression was associated with highly proliferative and aggressive breast cancer that was highly immunogenic with better response to PARP inhibitors in ER-positive patients. BRCA2 gene expression may become a candidate marker for aggressive biology and to tailor specific treatment strategies in the future.

Related Products

Cat.No. Product Name Information
S8828 Gboxin Gboxin is an inhibitor of oxidative phosphorylation in cancer cells. Gboxin inhibits the activity of F0F1 ATP synthase. It specifically inhibits the growth of primary mouse and human glioblastoma cells but not that of mouse embryonic fibroblasts or neonatal astrocytes.

Related Targets

OXPHOS ATPase