Eman A Al-Sharabass, Motawa E El-Houseini, Heba Effat, Sherif Abdelaziz Ibrahim, Mona S Abdellateif
{"title":"PDL-1通路及相关微rna作为乳腺癌诊断标志物的临床潜力","authors":"Eman A Al-Sharabass, Motawa E El-Houseini, Heba Effat, Sherif Abdelaziz Ibrahim, Mona S Abdellateif","doi":"10.1186/s10020-025-01137-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint pathways play important roles in breast cancer (BC) pathogenesis and therapy.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"106"},"PeriodicalIF":6.0000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921724/pdf/","citationCount":"0","resultStr":"{\"title\":\"The clinical potential of PDL-1 pathway and some related micro-RNAs as promising diagnostic markers for breast cancer.\",\"authors\":\"Eman A Al-Sharabass, Motawa E El-Houseini, Heba Effat, Sherif Abdelaziz Ibrahim, Mona S Abdellateif\",\"doi\":\"10.1186/s10020-025-01137-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immune checkpoint pathways play important roles in breast cancer (BC) pathogenesis and therapy.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":18813,\"journal\":{\"name\":\"Molecular Medicine\",\"volume\":\"31 1\",\"pages\":\"106\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-03-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921724/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s10020-025-01137-1\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10020-025-01137-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The clinical potential of PDL-1 pathway and some related micro-RNAs as promising diagnostic markers for breast cancer.
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.
期刊介绍：
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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