Background:Prostate adenocarcinoma(PRAD)is one of the most commonly diagnosed cancers in men.Expanding evidence suggests a significant association between cancer progression and RNA modifications.However,our knowledge...Background:Prostate adenocarcinoma(PRAD)is one of the most commonly diagnosed cancers in men.Expanding evidence suggests a significant association between cancer progression and RNA modifications.However,our knowledge of the link between m^(5)C and hm^(5)C pathways with PRAD is limited.Therefore,we aimed to explore the diagnostic and prognostic values of m^(5)C and hm^(5)C regulators in PRAD.Methods:In this study,genetic alterations in m^(5)C and hm^(5)C regulators were identified using publicly available databases.Expression levels of regulators in PRAD samples were retrieved via the RTCGA package in the R environment.Differentially expressed genes in these pathways between tumor and non-tumor samples were identified using the R‘limma’package.Correlation among m^(5)C and hm^(5)C pathway members was examined employing the‘Hmisc’package in R.We utilized the‘survminer’package in R for applying the Kaplan-Meier method to estimate the overall survival rate of m^(5)C and hm^(5)C regulators.The discrimination power of selected regulators between tumor and non-tumor samples was analyzed by the receiver operating characteristic curve.Furthermore,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were carried out to enrich the affected biological processes and pathways.Results:Differentially expressed genes in these pathways between tumor and non-tumor samples,correlation among m^(5)C and hm^(5)C pathway members,and prognostic value of the regulators were evaluated.Obtained results unveiled the mRNA level differences as the key genetic alterations for m^(5)C and hm^(5)C regulators between tumor and non-tumor samples.UHRF1,TET3,and NEIL1 were significantly upregulated in tumor samples,whereas MECP2 and EGR1 were significantly downregulated for m^(5)C and hm^(5)C regulators.UHRF1,DNMT1,NSUN2,NSUN4,C1orf77,C3orf37,WDR77,NEIL1,and TDG genes were identified as candidate prognostic markers of overall survival.The upregulated genes in patient samples with genetic alterations in m^(5)C and hm^(5)C pathways enriched cell cycle-related processes.Conclusion:In summary,our findings suggest that the m^(5)C and hm^(5)C regulators might play a role in PRAD development by activation of proliferation,and the UHRF1,NSUN2,and NEIL1 genes have the potential to be utilized as clinical biomarkers.Established correlative relationships require experimental validation through functional studies in prostate cancer cell lines.展开更多
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
目的探究血清分泌型卷曲相关蛋白5(secreted frizzled related protein 5,SFRP-5)、C-X-C基序趋化因子配体16(C-X-C motif chemokine ligand 16,CXCL16)对心肌梗死患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后...目的探究血清分泌型卷曲相关蛋白5(secreted frizzled related protein 5,SFRP-5)、C-X-C基序趋化因子配体16(C-X-C motif chemokine ligand 16,CXCL16)对心肌梗死患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后心力衰竭(heart failure,HF)发生的预测价值。方法选取2022年6月至2024年1月于保定市第二中心医院实施PCI治疗的心肌梗死患者152例为研究对象。术后随访1年,根据患者是否发生HF分为HF组和(n=47)非HF组(n=105)。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测PCI治疗前患者血清SFRP-5、CXCL16的浓度;采用多因素Logistic回归法分析影响心肌梗死患者PCI治疗后HF发生的因素;绘制受试者工作特征(receiver operating characteristic,ROC)曲线分析血清SFRP-5、CXCL16浓度对心肌梗死患者PCI治疗后HF发生的预测价值。结果与非HF组患者比较,HF组患者性别、体质量指数(body mass index,BMI)、吸烟史、原发性高血压(高血压)史、糖尿病史、收缩压、舒张压及血肌酐(serum creatinine,Scr)、空腹血糖、总胆固醇浓度比较,差异无统计学意义(P>0.05);血清SFRP-5浓度显著降低,年龄及纤维蛋白原、CXCL16浓度浓度显著升高,差异有统计学意义(P<0.05)。年龄(OR=1.712)、纤维蛋白原(OR=2.240)、CXCL16浓度升高(OR=3.948),SFRP-5浓度降低(OR=0.284)均是影响心肌梗死患者PCI治疗后HF发生的危险因素(P<0.05)。血清SFRP-5、CXCL16浓度单独预测心肌梗死患者PCI治疗后HF发生的曲线下面积(area under the curve,AUC)分别为0.698(95%CI:0.619~0.770)、0.801(95%CI:0.729~0.861),二者联合预测的AUC为0.952(95%CI:0.905~0.980),灵敏度为91.49%,特异度为91.43%。联合预测价值显著高于单一指标预测(Z_(三者联合-SFRP-5)=5.839、Z_(三者联合-CXCL16)=3.564,P<0.05)。结论血清SFRP-5、CXCL16浓度对心肌梗死患者PCI治疗后HF发生具有一定的预测价值,且二者联合的预测价值更高。展开更多
基金Health Institutes of Turkey(TUSEBProject No.TA01-4213)for the financial support of the present study.
文摘Background:Prostate adenocarcinoma(PRAD)is one of the most commonly diagnosed cancers in men.Expanding evidence suggests a significant association between cancer progression and RNA modifications.However,our knowledge of the link between m^(5)C and hm^(5)C pathways with PRAD is limited.Therefore,we aimed to explore the diagnostic and prognostic values of m^(5)C and hm^(5)C regulators in PRAD.Methods:In this study,genetic alterations in m^(5)C and hm^(5)C regulators were identified using publicly available databases.Expression levels of regulators in PRAD samples were retrieved via the RTCGA package in the R environment.Differentially expressed genes in these pathways between tumor and non-tumor samples were identified using the R‘limma’package.Correlation among m^(5)C and hm^(5)C pathway members was examined employing the‘Hmisc’package in R.We utilized the‘survminer’package in R for applying the Kaplan-Meier method to estimate the overall survival rate of m^(5)C and hm^(5)C regulators.The discrimination power of selected regulators between tumor and non-tumor samples was analyzed by the receiver operating characteristic curve.Furthermore,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were carried out to enrich the affected biological processes and pathways.Results:Differentially expressed genes in these pathways between tumor and non-tumor samples,correlation among m^(5)C and hm^(5)C pathway members,and prognostic value of the regulators were evaluated.Obtained results unveiled the mRNA level differences as the key genetic alterations for m^(5)C and hm^(5)C regulators between tumor and non-tumor samples.UHRF1,TET3,and NEIL1 were significantly upregulated in tumor samples,whereas MECP2 and EGR1 were significantly downregulated for m^(5)C and hm^(5)C regulators.UHRF1,DNMT1,NSUN2,NSUN4,C1orf77,C3orf37,WDR77,NEIL1,and TDG genes were identified as candidate prognostic markers of overall survival.The upregulated genes in patient samples with genetic alterations in m^(5)C and hm^(5)C pathways enriched cell cycle-related processes.Conclusion:In summary,our findings suggest that the m^(5)C and hm^(5)C regulators might play a role in PRAD development by activation of proliferation,and the UHRF1,NSUN2,and NEIL1 genes have the potential to be utilized as clinical biomarkers.Established correlative relationships require experimental validation through functional studies in prostate cancer cell lines.
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.
文摘目的探究血清分泌型卷曲相关蛋白5(secreted frizzled related protein 5,SFRP-5)、C-X-C基序趋化因子配体16(C-X-C motif chemokine ligand 16,CXCL16)对心肌梗死患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后心力衰竭(heart failure,HF)发生的预测价值。方法选取2022年6月至2024年1月于保定市第二中心医院实施PCI治疗的心肌梗死患者152例为研究对象。术后随访1年,根据患者是否发生HF分为HF组和(n=47)非HF组(n=105)。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测PCI治疗前患者血清SFRP-5、CXCL16的浓度;采用多因素Logistic回归法分析影响心肌梗死患者PCI治疗后HF发生的因素;绘制受试者工作特征(receiver operating characteristic,ROC)曲线分析血清SFRP-5、CXCL16浓度对心肌梗死患者PCI治疗后HF发生的预测价值。结果与非HF组患者比较,HF组患者性别、体质量指数(body mass index,BMI)、吸烟史、原发性高血压(高血压)史、糖尿病史、收缩压、舒张压及血肌酐(serum creatinine,Scr)、空腹血糖、总胆固醇浓度比较,差异无统计学意义(P>0.05);血清SFRP-5浓度显著降低,年龄及纤维蛋白原、CXCL16浓度浓度显著升高,差异有统计学意义(P<0.05)。年龄(OR=1.712)、纤维蛋白原(OR=2.240)、CXCL16浓度升高(OR=3.948),SFRP-5浓度降低(OR=0.284)均是影响心肌梗死患者PCI治疗后HF发生的危险因素(P<0.05)。血清SFRP-5、CXCL16浓度单独预测心肌梗死患者PCI治疗后HF发生的曲线下面积(area under the curve,AUC)分别为0.698(95%CI:0.619~0.770)、0.801(95%CI:0.729~0.861),二者联合预测的AUC为0.952(95%CI:0.905~0.980),灵敏度为91.49%,特异度为91.43%。联合预测价值显著高于单一指标预测(Z_(三者联合-SFRP-5)=5.839、Z_(三者联合-CXCL16)=3.564,P<0.05)。结论血清SFRP-5、CXCL16浓度对心肌梗死患者PCI治疗后HF发生具有一定的预测价值,且二者联合的预测价值更高。
