AIM:To understand the implication of GATA-4 and GATA-5 methylation in gastric carcinogenesis.METHODS: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biops...AIM:To understand the implication of GATA-4 and GATA-5 methylation in gastric carcinogenesis.METHODS: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biopsies from 45 outpatients, gastric dysplasia [low-grade gastric intraepithelial neoplasia (GIN), n = 30; indefinite, n = 77], and 80 paired spo- radic gastric carcinomas (SGC) as well as the adjacent non-neoplastic gastric tissues was analyzed by methylation specific polymerase chain reaction (MSP) and confirmed by denatured high performance liquid chromatography (DHPLC). Immunohistochemical staining was used to detect protein expression. The correlation between GATA-4 and GATA-5 methylation and clinicopathological characteristics of patients including Helicobacter pylori (H. pylori) infection was analyzed.RESULTS:GATA-4 and GATA-5 methylation was frequently observed in SGCs (53.8% and 61.3%, respectively) and their corresponding normal tissues (41.3% and 46.3%) by MSP. The result of MSP was consistent with that of DHPLC. Loss of both GATA-4 and GATA-5 proteins was associated with their methylation in SGCs (P = 0.01). Moreover, a high frequency of GATA-4 and GATA-5 methylation was found in both gastric low-grade GIN (57.1% and 69.0%) and indefinite for dysplasia (42.9% and 46.7%), respectively. However, GATA-4 and GATA-5 methylation was detected only in 4/32 (12.5%) and 3/39 (7.7%) of normal gastric biopsies. GATA-4 methylation in both normal gastric mucosa and low-grade GIN was also significantly associated with H. pylori infection (P=0.023 and 0.027, two-sides).CONCLUSION: Epigenetic inactivation of GATA-4 (and GATA-5) by methylation of CpG islands is an early freuent event during gastric carcinogenesis and is significantly correlated with H. pylori infection.展开更多
AIM:To investigate GATA5,SFRP2,and ITGA4 methylation in plasma DNA as noninvasive biomarkers for colorectal cancer(CRC) or adenomas.METHODS:There were 57 CRC patients,30 adenomas patients,and 47 control patients enrol...AIM:To investigate GATA5,SFRP2,and ITGA4 methylation in plasma DNA as noninvasive biomarkers for colorectal cancer(CRC) or adenomas.METHODS:There were 57 CRC patients,30 adenomas patients,and 47 control patients enrolled in this study.Methylation-specific polymerase chain reaction was used to determine the promoter methylation status of GATA5,SFRP2,and ITGA4 genes in plasma DNA,and their association with clinical outcome in CRC.The predictive ability of GATA5,SFRP2,and ITGA4 methylation,individually or in combination,to detect CRC or adenomas was further analyzed.RESULTS:Hypermethylated GATA5 was detected in plasma in 61.4%(35/57) of CRC cases,43.33%(13/30) of adenoma cases,and 21.28%(10/47) of control cases.The hypermethylation of SFRP2 was detected in 54.39%(31/57),40.00%(12/30),and 27.66%(13/47) in plasma samples from CRC,adenomas,and controls,respectively.ITGA4 methylation was detected in 36.84%(21/57) of plasma samples of CRC patients and in 30.00%(9/30) of plasma samples from patients with colorectal adenomas,and the specificity of this individual biomarker was 80.85%(9/47).Moreover,GATA5 methylation in the plasma was significantly correlated with larger tumor size(P =0.019),differentiation status(P =0.038),TNM stage(P =0.008),and lymph node metastasis(P =0.008).SFRP2 and ITGA4 methylation in plasma significantly correlated with differentiation status(SFRP2,P =0.012; ITGA4,P =0.007),TNM stage(SFRP2,P =0.034; ITGA4,P =0.021),and lymph node metastasis(SFRP2,P =0.034; ITGA4,P =0.021).From the perspective of predictive power and cost-performance,using GATA5 and SFRP2 together as methylation markers seemed the most favorable predictor for CRC(OR =8.06;95%CI:2.54-25.5; P < 0.01) and adenomas(OR =3.35; 95%CI:1.29-8.71; P =0.012).CONCLUSION:A combination of GATA5 and SFRP2 methylation could be promising as a marker for the detection and diagnosis of CRC and adenomas.展开更多
目的研究氟西汀(Fluoxetine,Flu)抑制野百合碱(Monocrotaline,MCT)诱导的大鼠右心室肥厚与(GATA binding protein 4)结合蛋白4(GATA-4)表达的关系。方法建立MCT诱导的慢性肺动脉高压大鼠模型。灌胃给予大鼠不同剂量的Flu,检测右心室肥...目的研究氟西汀(Fluoxetine,Flu)抑制野百合碱(Monocrotaline,MCT)诱导的大鼠右心室肥厚与(GATA binding protein 4)结合蛋白4(GATA-4)表达的关系。方法建立MCT诱导的慢性肺动脉高压大鼠模型。灌胃给予大鼠不同剂量的Flu,检测右心室肥厚指标和心室GATA-4蛋白表达水平。结果MCT诱导的大鼠右心指数及右心室GATA-4蛋白表达均比正常对照组显著增加,Flu剂量依赖地抑制了右心指数及右心室GATA-4表达增加,而各组间左心室和室间隔的GATA-4表达没有明显变化。结论选择性5-羟色胺再摄取抑制剂Flu抑制MCT诱导的大鼠右心室肥厚可能与抑制GATA-4表达有关。展开更多
基金Supported by (in part) National High Technology R & D Program,No.2006AA02A402National High Technology R & D Program,No.2010CB529300-GNSFC Grant,No.30921140311 to Deng DJ
文摘AIM:To understand the implication of GATA-4 and GATA-5 methylation in gastric carcinogenesis.METHODS: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biopsies from 45 outpatients, gastric dysplasia [low-grade gastric intraepithelial neoplasia (GIN), n = 30; indefinite, n = 77], and 80 paired spo- radic gastric carcinomas (SGC) as well as the adjacent non-neoplastic gastric tissues was analyzed by methylation specific polymerase chain reaction (MSP) and confirmed by denatured high performance liquid chromatography (DHPLC). Immunohistochemical staining was used to detect protein expression. The correlation between GATA-4 and GATA-5 methylation and clinicopathological characteristics of patients including Helicobacter pylori (H. pylori) infection was analyzed.RESULTS:GATA-4 and GATA-5 methylation was frequently observed in SGCs (53.8% and 61.3%, respectively) and their corresponding normal tissues (41.3% and 46.3%) by MSP. The result of MSP was consistent with that of DHPLC. Loss of both GATA-4 and GATA-5 proteins was associated with their methylation in SGCs (P = 0.01). Moreover, a high frequency of GATA-4 and GATA-5 methylation was found in both gastric low-grade GIN (57.1% and 69.0%) and indefinite for dysplasia (42.9% and 46.7%), respectively. However, GATA-4 and GATA-5 methylation was detected only in 4/32 (12.5%) and 3/39 (7.7%) of normal gastric biopsies. GATA-4 methylation in both normal gastric mucosa and low-grade GIN was also significantly associated with H. pylori infection (P=0.023 and 0.027, two-sides).CONCLUSION: Epigenetic inactivation of GATA-4 (and GATA-5) by methylation of CpG islands is an early freuent event during gastric carcinogenesis and is significantly correlated with H. pylori infection.
基金Supported by Social Development Foundation of Ningbo,No.2011C50022Natural Science Foundation of Ningbo,No.2012A610212the Scientific Innovation Team Project of Ningbo,No.2013B82010
文摘AIM:To investigate GATA5,SFRP2,and ITGA4 methylation in plasma DNA as noninvasive biomarkers for colorectal cancer(CRC) or adenomas.METHODS:There were 57 CRC patients,30 adenomas patients,and 47 control patients enrolled in this study.Methylation-specific polymerase chain reaction was used to determine the promoter methylation status of GATA5,SFRP2,and ITGA4 genes in plasma DNA,and their association with clinical outcome in CRC.The predictive ability of GATA5,SFRP2,and ITGA4 methylation,individually or in combination,to detect CRC or adenomas was further analyzed.RESULTS:Hypermethylated GATA5 was detected in plasma in 61.4%(35/57) of CRC cases,43.33%(13/30) of adenoma cases,and 21.28%(10/47) of control cases.The hypermethylation of SFRP2 was detected in 54.39%(31/57),40.00%(12/30),and 27.66%(13/47) in plasma samples from CRC,adenomas,and controls,respectively.ITGA4 methylation was detected in 36.84%(21/57) of plasma samples of CRC patients and in 30.00%(9/30) of plasma samples from patients with colorectal adenomas,and the specificity of this individual biomarker was 80.85%(9/47).Moreover,GATA5 methylation in the plasma was significantly correlated with larger tumor size(P =0.019),differentiation status(P =0.038),TNM stage(P =0.008),and lymph node metastasis(P =0.008).SFRP2 and ITGA4 methylation in plasma significantly correlated with differentiation status(SFRP2,P =0.012; ITGA4,P =0.007),TNM stage(SFRP2,P =0.034; ITGA4,P =0.021),and lymph node metastasis(SFRP2,P =0.034; ITGA4,P =0.021).From the perspective of predictive power and cost-performance,using GATA5 and SFRP2 together as methylation markers seemed the most favorable predictor for CRC(OR =8.06;95%CI:2.54-25.5; P < 0.01) and adenomas(OR =3.35; 95%CI:1.29-8.71; P =0.012).CONCLUSION:A combination of GATA5 and SFRP2 methylation could be promising as a marker for the detection and diagnosis of CRC and adenomas.
文摘目的研究氟西汀(Fluoxetine,Flu)抑制野百合碱(Monocrotaline,MCT)诱导的大鼠右心室肥厚与(GATA binding protein 4)结合蛋白4(GATA-4)表达的关系。方法建立MCT诱导的慢性肺动脉高压大鼠模型。灌胃给予大鼠不同剂量的Flu,检测右心室肥厚指标和心室GATA-4蛋白表达水平。结果MCT诱导的大鼠右心指数及右心室GATA-4蛋白表达均比正常对照组显著增加,Flu剂量依赖地抑制了右心指数及右心室GATA-4表达增加,而各组间左心室和室间隔的GATA-4表达没有明显变化。结论选择性5-羟色胺再摄取抑制剂Flu抑制MCT诱导的大鼠右心室肥厚可能与抑制GATA-4表达有关。
