Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterize...Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterized.This study aims to systematically explore the expression patterns,clinical significance,and immune-related functions of NUDT19 in various cancer types through multi-omics analysis,further revealing its potential role in cancer,particularly its functional and therapeutic target value in leukemia.Methods To achieve this goal,various bioinformatics approaches were employed to evaluate the expression patterns,clinical significance,and immune-related functions of NUDT19 in tumors and normal tissues.Additionally,we analyzed the mutation characteristics of NUDT19 and its relationship with epigenetic modifications.Using the single-cell analysis tool SingleCellBase,we explored the distribution of NUDT19 across different cell subpopulations in tumors.To validate these findings,qRT-PCR was used to measure NUDT19 expression levels in specific tumor cell lines,and we established acute myeloid leukemia(AML)cell lines(HL-60 and THP-1)to conduct NUDT19 knockdown and overexpression experiments,assessing its effects on leukemia cell proliferation,apoptosis,and invasion.Results Pan-cancer analysis revealed the dysregulated expression of NUDT19 across multiple cancer types,which was closely associated with poor prognosis,clinical staging,and diagnostic markers.Furthermore,NUDT19 was significantly correlated with tumor biomarkers,immune-related genes,and immune cell infiltration in different cancers.Mutation analysis showed that multiple mutations in NUDT19 were significantly associated with epigenetic changes.Single-cell analysis revealed the heterogeneity of NUDT19 expression in cancer cells,suggesting its potentially diverse functional roles in different cell subpopulations.qRT-PCR experiments confirmed the significant upregulation of NUDT19 in various tumor cell lines.In AML cell lines,NUDT19 knockdown led to reduced cell proliferation and invasion,with increased apoptosis,while NUDT19 overexpression significantly enhanced cell proliferation and invasion while reducing apoptosis.Conclusion This study demonstrates the diverse roles of NUDT19 in various cancer types,with a particularly prominent functional role in leukemia.NUDT19 is not only associated with tumor initiation and progression but may also influence cancer progression through the regulation of immune microenvironment and epigenetic mechanisms.Our research highlights the potential of NUDT19 as a therapeutic target,particularly for targeted therapies in malignancies such as leukemia,with significant clinical application prospects.展开更多
目的 Meta分析探讨NUDT15 c.415C>T位点单核苷酸多态性(SNP)与巯嘌呤类药物所致患者白细胞减少的相关性。方法检索Pubmed、EMbase、中国知网、万方数据库等数据库,同时利用计算机检索、文献追溯等途径收集国内外公开发表的关于NUDT1...目的 Meta分析探讨NUDT15 c.415C>T位点单核苷酸多态性(SNP)与巯嘌呤类药物所致患者白细胞减少的相关性。方法检索Pubmed、EMbase、中国知网、万方数据库等数据库,同时利用计算机检索、文献追溯等途径收集国内外公开发表的关于NUDT15与巯嘌呤类药物所致白细胞减少的相关性研究文献。检索的文献为截止到2018年2月28日已发表的所有文献。采用NOS标准评价纳入各个原始文献的质量。采用OR值和95%置信区间(CI)来评价NUDT15 c.415C> T和白细胞减少之间的关系。结果纳入7篇研究,共有1 198个接受巯嘌呤类药物治疗的患者。Meta分析结果如下:显性遗传模型(CT+TT vs CC,OR=9.29,95%CI:6.43～13.44,P=0.0001),纯合子模型(TT vs CC,OR=37.32,95%CI:14.199～98.10,P=0.0009),杂合子模型(CT vs CC,OR=7.42,95%CI:5.05～10.88,P=0.0005),隐性遗传模型(TT vs CT,OR=8.79,95%CI:3.497～22.12)。按所有纳入研究的对象Meta分析结果显示,携带T等位基因的NUDT15 c.415C> T与巯嘌呤所导致的白细胞减少的发生具有强相关性(P<0.05)。结论对于巯嘌呤来说,在亚洲人口中,NUDT15 c.415C> T可能是一个高度可信的药物基因预测者。由于该研究纳入的文献数量较少,相关结果需要更多研究予以验证。展开更多
AIM To observe gene polymorphisms of TPMT and NUDT15,and compare their predictive value for azathioprine(AZA)-induced leukopenia in inflammatory bowel disease(IBD).METHODS This study enrolled 219 patients diagnosed wi...AIM To observe gene polymorphisms of TPMT and NUDT15,and compare their predictive value for azathioprine(AZA)-induced leukopenia in inflammatory bowel disease(IBD).METHODS This study enrolled 219 patients diagnosed with IBD in Xiangya Hospital,Central South University,Changsha,China from February 2016 to November 2017.Peripheral blood of all patients was collected to detect their genotypes of TPMT and NUDT15 by pyrosequencing at the Department of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics,Xiangya Hospital.Eighty patients were treated with AZA according to the disease condition.During the first month,patients who received AZA underwent routine blood tests and liver function tests once a week.The endpoint of the study was leukopenia induced by AZA.By analyzing patient characteristics,genotypes and leukopenia induced by drug use,we found the risk factors associated with AZA-induced leukopenia.RESULTS There were 219 patients with IBD(160 men and 59 women),including 39 who were confirmed with ulcerative colitis(UC),176 with Crohn's disease(CD)and 4 with undetermined IBD(UIBD).There were 44 patients(20.1%)with mutant genotype of NUDT15(C/T);among them,16 received AZA,and 8(50%)developed leukopenia.There were 175 patients(79.7%)with wild genotype of NUDT15(C/C);among them,64 received AZA,and 11(17.2%)developed leukopenia.A significant difference was found between NUDT15 C/T and its wild-type C/C(P=0.004).There were only 3 patients with TPMT mutant genotype of A/G(1.4%)who participated in the research,and 1 of them was treated with AZA and developed leukopenia.The remaining 216 patients(98.6%)were found to bear the wild genotype of TPMT(A/A);among them,79 patients received AZA,and 18(22.8%)developed leukopenia,and there was no significant difference from those with A/G(P=0.071).The frequency of TPMT mutation was 1.4%,and NUDT15 mutation rate was significantly higher and reached 20.1%(P=0.000).Therefore,NUDT15 gene polymorphism was obviously a better biomarker than TPMT gene polymorphism in the prediction of AZA-induced leukopenia.CONCLUSION Mutation rate of NUDT15 in Chinese IBD patients is higher than that of TPMT.NUDT15 polymorphism is a better predictor for AZA-induced leukopenia than TPMT polymorphism.展开更多
文摘Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterized.This study aims to systematically explore the expression patterns,clinical significance,and immune-related functions of NUDT19 in various cancer types through multi-omics analysis,further revealing its potential role in cancer,particularly its functional and therapeutic target value in leukemia.Methods To achieve this goal,various bioinformatics approaches were employed to evaluate the expression patterns,clinical significance,and immune-related functions of NUDT19 in tumors and normal tissues.Additionally,we analyzed the mutation characteristics of NUDT19 and its relationship with epigenetic modifications.Using the single-cell analysis tool SingleCellBase,we explored the distribution of NUDT19 across different cell subpopulations in tumors.To validate these findings,qRT-PCR was used to measure NUDT19 expression levels in specific tumor cell lines,and we established acute myeloid leukemia(AML)cell lines(HL-60 and THP-1)to conduct NUDT19 knockdown and overexpression experiments,assessing its effects on leukemia cell proliferation,apoptosis,and invasion.Results Pan-cancer analysis revealed the dysregulated expression of NUDT19 across multiple cancer types,which was closely associated with poor prognosis,clinical staging,and diagnostic markers.Furthermore,NUDT19 was significantly correlated with tumor biomarkers,immune-related genes,and immune cell infiltration in different cancers.Mutation analysis showed that multiple mutations in NUDT19 were significantly associated with epigenetic changes.Single-cell analysis revealed the heterogeneity of NUDT19 expression in cancer cells,suggesting its potentially diverse functional roles in different cell subpopulations.qRT-PCR experiments confirmed the significant upregulation of NUDT19 in various tumor cell lines.In AML cell lines,NUDT19 knockdown led to reduced cell proliferation and invasion,with increased apoptosis,while NUDT19 overexpression significantly enhanced cell proliferation and invasion while reducing apoptosis.Conclusion This study demonstrates the diverse roles of NUDT19 in various cancer types,with a particularly prominent functional role in leukemia.NUDT19 is not only associated with tumor initiation and progression but may also influence cancer progression through the regulation of immune microenvironment and epigenetic mechanisms.Our research highlights the potential of NUDT19 as a therapeutic target,particularly for targeted therapies in malignancies such as leukemia,with significant clinical application prospects.
文摘目的 Meta分析探讨NUDT15 c.415C>T位点单核苷酸多态性(SNP)与巯嘌呤类药物所致患者白细胞减少的相关性。方法检索Pubmed、EMbase、中国知网、万方数据库等数据库,同时利用计算机检索、文献追溯等途径收集国内外公开发表的关于NUDT15与巯嘌呤类药物所致白细胞减少的相关性研究文献。检索的文献为截止到2018年2月28日已发表的所有文献。采用NOS标准评价纳入各个原始文献的质量。采用OR值和95%置信区间(CI)来评价NUDT15 c.415C> T和白细胞减少之间的关系。结果纳入7篇研究,共有1 198个接受巯嘌呤类药物治疗的患者。Meta分析结果如下:显性遗传模型(CT+TT vs CC,OR=9.29,95%CI:6.43～13.44,P=0.0001),纯合子模型(TT vs CC,OR=37.32,95%CI:14.199～98.10,P=0.0009),杂合子模型(CT vs CC,OR=7.42,95%CI:5.05～10.88,P=0.0005),隐性遗传模型(TT vs CT,OR=8.79,95%CI:3.497～22.12)。按所有纳入研究的对象Meta分析结果显示,携带T等位基因的NUDT15 c.415C> T与巯嘌呤所导致的白细胞减少的发生具有强相关性(P<0.05)。结论对于巯嘌呤来说,在亚洲人口中,NUDT15 c.415C> T可能是一个高度可信的药物基因预测者。由于该研究纳入的文献数量较少,相关结果需要更多研究予以验证。
基金Supported by National Natural Science Foundation of China,No.81370547 and No.81400642
文摘AIM To observe gene polymorphisms of TPMT and NUDT15,and compare their predictive value for azathioprine(AZA)-induced leukopenia in inflammatory bowel disease(IBD).METHODS This study enrolled 219 patients diagnosed with IBD in Xiangya Hospital,Central South University,Changsha,China from February 2016 to November 2017.Peripheral blood of all patients was collected to detect their genotypes of TPMT and NUDT15 by pyrosequencing at the Department of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics,Xiangya Hospital.Eighty patients were treated with AZA according to the disease condition.During the first month,patients who received AZA underwent routine blood tests and liver function tests once a week.The endpoint of the study was leukopenia induced by AZA.By analyzing patient characteristics,genotypes and leukopenia induced by drug use,we found the risk factors associated with AZA-induced leukopenia.RESULTS There were 219 patients with IBD(160 men and 59 women),including 39 who were confirmed with ulcerative colitis(UC),176 with Crohn's disease(CD)and 4 with undetermined IBD(UIBD).There were 44 patients(20.1%)with mutant genotype of NUDT15(C/T);among them,16 received AZA,and 8(50%)developed leukopenia.There were 175 patients(79.7%)with wild genotype of NUDT15(C/C);among them,64 received AZA,and 11(17.2%)developed leukopenia.A significant difference was found between NUDT15 C/T and its wild-type C/C(P=0.004).There were only 3 patients with TPMT mutant genotype of A/G(1.4%)who participated in the research,and 1 of them was treated with AZA and developed leukopenia.The remaining 216 patients(98.6%)were found to bear the wild genotype of TPMT(A/A);among them,79 patients received AZA,and 18(22.8%)developed leukopenia,and there was no significant difference from those with A/G(P=0.071).The frequency of TPMT mutation was 1.4%,and NUDT15 mutation rate was significantly higher and reached 20.1%(P=0.000).Therefore,NUDT15 gene polymorphism was obviously a better biomarker than TPMT gene polymorphism in the prediction of AZA-induced leukopenia.CONCLUSION Mutation rate of NUDT15 in Chinese IBD patients is higher than that of TPMT.NUDT15 polymorphism is a better predictor for AZA-induced leukopenia than TPMT polymorphism.
