The clinical potential of PDL-1 pathway and some related micro-RNAs as promising diagnostic markers for breast cancer
Abstract Background Immune checkpoint pathways play important roles in breast cancer (BC) pathogenesis and therapy. Methods Expression levels of programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed death-ligand 1 (PD-L1), Forkhead box P3 (FOXP3), m...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
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| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10020-025-01137-1 |
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| Summary: | Abstract Background Immune checkpoint pathways play important roles in breast cancer (BC) pathogenesis and therapy. Methods Expression levels of programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed death-ligand 1 (PD-L1), Forkhead box P3 (FOXP3), miR-155, and miR-195 were assessed in the peripheral blood of 90 BC patients compared to 30 healthy controls using quantitative real-time PCR (qRt-PCR). The plasma level of soluble MHC class I chain related-protein B (MIC-B) protein was assessed using the enzyme linked immunosorbent assay (ELISA) technique. The data were correlated to the clinico-pathological characteristics of the patients. Results There was a significant increase in the expression levels of PDL-1 [17.59 (3.24–123), p < 0.001], CTLA-4 [23.34 (1.3–1267), p = 0.006], PD-1 [10.25 (1–280), p < 0.001], FOXP3 [11.5 (1–234.8), p = 0.001], miR-155 [87.3 (1.5–910), p < 0.001] in BC patients compared to normal controls. The miR-195 was significantly downregulated in BC patients [0.23 (0–0.98, p < 0.001]. The plasma level of MIC-B was significantly increased in the BC patients [0.941 (0.204–6.38) ng/ml], compared to the control group [0.351 (0.211–0.884) ng/mL, p < 0.00]. PDL-1, CTLA-4, PD-1, and FOXP3 achieved a specificity of 100% for distinguishing BC patients, at a sensitivity of 93.3%, 82.2%, 62.2%, and 71.1% respectively. The combined expression of PDL-1 and CTLA-4 scored a 100% sensitivity and 100% specificity for diagnosing BC (p < 0.001). The sensitivity, specificity, and AUC of miR-155 were 88.9%, 96.7%, and 0.934; respectively (p < 0.001). While those of miR-195 were 73.3%, 60%, and 0.716; respectively (p = 0.001). MIC-B expression showed a 77.8% sensitivity, 80% specificity, and 0.811 AUC at a cutoff of 1.17 ng/ml (p < 0.001). Combined expression of miR-155 and miR-195 achieved a sensitivity of 91.1%, a specificity of 96.7%, and AUC of 0.926 (p < 0.001). Multivariate analysis showed that PDL-1 (OR:13.825, p = 0.004), CTLA-4 (OR: 20.958, p = 0.010), PD-1(OR:10.550, p = 0.044), MIC-B (OR: 17.89, p = 0.003), miR-155 (OR: 211.356, P < 0.001), and miR-195(OR:0.006, P < 0.001) were considered as independent risk factors for BC. Conclusions The PB levels of PDL-1, CTLA-4, PD-1, FOXP3, MIC-B, miR-155, and miR-195 could be used as promising diagnostic markers for BC patients. |
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| ISSN: | 1528-3658 |