Fig. 7
From: Upregulated PARP1 confers breast cancer resistance to CDK4/6 inhibitors via YB-1 phosphorylation
Low ‘‘p-YB-1-PARP1’’ expression was linked to CDK4/6i sensitivity in breast cancer. A. The data from multiple immunofluorescence (MIF) assays indicated that p-YB-1 and PARP1 were coexpressed and colocalized in four representative breast cancer patients. The paraffin sections of the breast cancer patients were separately stained with p-YB-1 (red), PARP1 (green) and DAPI (blue). B–C The samples from 80 breast cancer patients were used for detection of p-YB-1 and PARP1 by IHC assay, the staining score ranged from 0 to 5. The 80 breast cancer patients were divided into HR + /HER2-, HR-/HER2-, HR-/HER2 + and HR + /HER2 + groups. D–E Typical images of high and low ‘‘p-YB-1/PARP1’’ expression in HR-/HER2- and HR + /HER2- patients are shown, and the staining results came from the same position of successive slices. F–G The patients were divided into four groups: p-YB-1L + PARP1L, p-YB-1L + PARP1H, p-YB-1H + PARP1L, and p-YB-1H + PARP1H groups, based on the expression of p-YB-1 and PARP1. The percentage of the high PARP1 group accounted for 100% of the high p-YB-1 group. H–J The scatter plots of the data clearly indicated that PARP1 positively correlated with p-YB-1 in the BC (n = 90, r = 0.6234, p < 0.0001***), HR + /HER2- (n = 52, r = 0.3556, p = 0.0097**) and HR-/HER2-(n = 13, r = 0.7673, p = 0.0022**) groups. K–L Patients in the low p-YB-1 group accounted for approximately 91% of CDK4/6i-sensitive clinical patients. In contrast, the patients with high p-YB-1 levels accounted for approximately 77% of CDK4/6i-resistant TNBC clinical patients. The results presented have been repeated in 3 biological replicates. Data, means ± SEMs, *, P < 0.05, **, P < 0.01, ***, P < 0.001.