Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integ...Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.展开更多
Non-small cell lung cancer(NSCLC)is a leading cause of cancer-related mortality worldwide1-3.While radioimmuno-therapy shows promise in boosting antitumor immunity,the clinical outcomes have been inconsistent4 and are...Non-small cell lung cancer(NSCLC)is a leading cause of cancer-related mortality worldwide1-3.While radioimmuno-therapy shows promise in boosting antitumor immunity,the clinical outcomes have been inconsistent4 and are often lim-ited by the immunosuppressive tumor microenvironment(TME).Cyclooxygenase(COX)-2 and the COX-2 downstream product,prostaglandin E2(PGE2),are increasingly implicated in immune escape5,6 but the impact on radioimmunother-apy efficacy has not been explored.TCF1-expressing CD8+T cells demonstrate defining functional properties of progeni-tor-exhausted T cells,including clonal expansion through self-renewal capacity and multipotent differentiation toward terminal effector phenotypes,while maintaining long-term persistence critical for sustaining antitumor immunity7-9.Given the central role in anti-tumor immune maintenance,TCF1+CD8+T cells are likely critical to radioimmunotherapy efficacy10.The role of COX-2 inhibition in enhancing the effi-cacy of radioimmunotherapy efficacy in NSCLC was investi-gated in the current study.展开更多
基金supported by grants from the Guangxi Natural Science Foundation(2024GXNSFAA010150)the Guangdong Basic and Applied Basic Research Foundation(2022A1515111167).
文摘Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.
基金funded by the National Natural Science Foundation of China(Grant Nos.82030082 and 82272845)the Natural Science Foundation of Shandong Province(Grant No.ZR2023LZL001).
文摘Non-small cell lung cancer(NSCLC)is a leading cause of cancer-related mortality worldwide1-3.While radioimmuno-therapy shows promise in boosting antitumor immunity,the clinical outcomes have been inconsistent4 and are often lim-ited by the immunosuppressive tumor microenvironment(TME).Cyclooxygenase(COX)-2 and the COX-2 downstream product,prostaglandin E2(PGE2),are increasingly implicated in immune escape5,6 but the impact on radioimmunother-apy efficacy has not been explored.TCF1-expressing CD8+T cells demonstrate defining functional properties of progeni-tor-exhausted T cells,including clonal expansion through self-renewal capacity and multipotent differentiation toward terminal effector phenotypes,while maintaining long-term persistence critical for sustaining antitumor immunity7-9.Given the central role in anti-tumor immune maintenance,TCF1+CD8+T cells are likely critical to radioimmunotherapy efficacy10.The role of COX-2 inhibition in enhancing the effi-cacy of radioimmunotherapy efficacy in NSCLC was investi-gated in the current study.
