Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancer
Abstract Background Triple-negative breast cancer (TNBC) is among the most aggressive forms of breast cancer, characterized by a dismal prognosis. In the absence of drug-targetable receptors, chemotherapy remains the sole systemic treatment alternative. Recent advancements in immunotherapy, particul...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12885-025-13428-1 |
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| author | Jingmin Che Bo Chen Xusheng Wang Baoe Liu Cuixiang Xu Huxia Wang Jingying Sun Qing Feng Xiangrong Zhao Zhangjun Song |
| author_facet | Jingmin Che Bo Chen Xusheng Wang Baoe Liu Cuixiang Xu Huxia Wang Jingying Sun Qing Feng Xiangrong Zhao Zhangjun Song |
| author_sort | Jingmin Che |
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| description | Abstract Background Triple-negative breast cancer (TNBC) is among the most aggressive forms of breast cancer, characterized by a dismal prognosis. In the absence of drug-targetable receptors, chemotherapy remains the sole systemic treatment alternative. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs) that target programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4), have provided renewed optimism for the treatment of patients with TNBC. Prior research has indicated that the expression level of the cell polarity protein discs large homolog 5 (DLG5) correlates with the malignant progression and prognosis of breast cancer; nevertheless, its influence on PD-L1 expression and its function in immunotherapy for TNBC require further investigation. Methods The hypoxia cell model was established by simulating the cell hypoxic microenvironment in the human SUM159 and MDA-MB-231 cell lines using cobalt II chloride (CoCl2). A combination of PD-L1 inhibitors and DLG5 RNA interference techniques was used, along with various methods including cell counting kit-8 (CCK-8), colony formation, wound healing, transwell migration, reverse transcription-quantitative real-time PCR (RT-qPCR), immunofluorescence, immunohistochemical staining (IHC), expression analysis from datasets and western blotting. These methods were employed to evaluate changes in cell proliferation, migration, and the expression levels of PD-L1 and DLG5. Additionally, the correlation between the expression of PD-L1 and DLG5 in clinical samples was analyzed. Results (1) In vitro experiments, a cellular hypoxia model was effectively established utilizing 150 µM CoCl₂. Under these conditions, cell clone formation, invasiveness, and migration rate were all significantly inhibited. (2) The expression levels of DLG5 and PD-L1 were significantly increased in both MDA-MB-231 and SUM159 cells following treatment with 150 µM CoCl₂. (3) Silencing DLG5 resulted in a considerable upregulation of PD-L1 expression in MDA-MB-231 and SUM159 cells under normoxic circumstances, but it was markedly downregulated under hypoxic settings. Inhibition of PD-L1 expression resulted in a considerable increase in DLG5 expression under normoxic conditions, but it decreased under hypoxic conditions. Correlation research demonstrated an inverse association between the expression of DLG5 and PD-L1 in TNBC tissues. Conclusion This study provides new theoretical evidence and potential therapeutic targets for the immunotherapy strategies of TNBC, holding significant clinical application value. |
| format | Article |
| id | doaj-art-d6bb9d6f1abd4d33a91552606de05445 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-d6bb9d6f1abd4d33a91552606de054452025-01-12T12:27:16ZengBMCBMC Cancer1471-24072025-01-0125111510.1186/s12885-025-13428-1Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancerJingmin Che0Bo Chen1Xusheng Wang2Baoe Liu3Cuixiang Xu4Huxia Wang5Jingying Sun6Qing Feng7Xiangrong Zhao8Zhangjun Song9Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s HospitalDepartment of Surgical Oncology, Shaanxi Provincial People’s HospitalDepartment of Surgical Oncology, Shaanxi Provincial People’s HospitalDepartment of Emergency Surgery, Shaanxi Provincial People’s HospitalShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s HospitalDepartment of Breast Disease Center, Shaanxi Provincial Tumor HospitalShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s HospitalShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s HospitalShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s HospitalShaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People’s HospitalAbstract Background Triple-negative breast cancer (TNBC) is among the most aggressive forms of breast cancer, characterized by a dismal prognosis. In the absence of drug-targetable receptors, chemotherapy remains the sole systemic treatment alternative. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs) that target programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4), have provided renewed optimism for the treatment of patients with TNBC. Prior research has indicated that the expression level of the cell polarity protein discs large homolog 5 (DLG5) correlates with the malignant progression and prognosis of breast cancer; nevertheless, its influence on PD-L1 expression and its function in immunotherapy for TNBC require further investigation. Methods The hypoxia cell model was established by simulating the cell hypoxic microenvironment in the human SUM159 and MDA-MB-231 cell lines using cobalt II chloride (CoCl2). A combination of PD-L1 inhibitors and DLG5 RNA interference techniques was used, along with various methods including cell counting kit-8 (CCK-8), colony formation, wound healing, transwell migration, reverse transcription-quantitative real-time PCR (RT-qPCR), immunofluorescence, immunohistochemical staining (IHC), expression analysis from datasets and western blotting. These methods were employed to evaluate changes in cell proliferation, migration, and the expression levels of PD-L1 and DLG5. Additionally, the correlation between the expression of PD-L1 and DLG5 in clinical samples was analyzed. Results (1) In vitro experiments, a cellular hypoxia model was effectively established utilizing 150 µM CoCl₂. Under these conditions, cell clone formation, invasiveness, and migration rate were all significantly inhibited. (2) The expression levels of DLG5 and PD-L1 were significantly increased in both MDA-MB-231 and SUM159 cells following treatment with 150 µM CoCl₂. (3) Silencing DLG5 resulted in a considerable upregulation of PD-L1 expression in MDA-MB-231 and SUM159 cells under normoxic circumstances, but it was markedly downregulated under hypoxic settings. Inhibition of PD-L1 expression resulted in a considerable increase in DLG5 expression under normoxic conditions, but it decreased under hypoxic conditions. Correlation research demonstrated an inverse association between the expression of DLG5 and PD-L1 in TNBC tissues. Conclusion This study provides new theoretical evidence and potential therapeutic targets for the immunotherapy strategies of TNBC, holding significant clinical application value.https://doi.org/10.1186/s12885-025-13428-1Triple-negative breast cancerDiscs large homolog 5Programmed cell death-ligand 1Hypoxia-inducible factor-1αCorrelation |
| spellingShingle | Jingmin Che Bo Chen Xusheng Wang Baoe Liu Cuixiang Xu Huxia Wang Jingying Sun Qing Feng Xiangrong Zhao Zhangjun Song Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancer BMC Cancer Triple-negative breast cancer Discs large homolog 5 Programmed cell death-ligand 1 Hypoxia-inducible factor-1α Correlation |
| title | Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancer |
| title_full | Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancer |
| title_fullStr | Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancer |
| title_full_unstemmed | Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancer |
| title_short | Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancer |
| title_sort | correlation analysis of dlg5 and pd l1 expression in triple negative breast cancer |
| topic | Triple-negative breast cancer Discs large homolog 5 Programmed cell death-ligand 1 Hypoxia-inducible factor-1α Correlation |
| url | https://doi.org/10.1186/s12885-025-13428-1 |
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