首页|子宫内膜异位症不同r-AFS分期患者血清Furin,TGF-β,VEGF,netrin-1水平表达及Furin基因P1启动区r2071410 C/T位点多态性分析

子宫内膜异位症不同r-AFS分期患者血清Furin,TGF-β,VEGF,netrin-1水平表达及Furin基因P1启动区r2071410 C/T位点多态性分析

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目的 了解子宫内膜异位症(endometriosis,EMT)不同r-AFS分期患者血清弗林蛋白酶(Furin)、肿瘤生长因子-β(tumor growth factor-β,TGF-β)、血管生长因子(vascular endothelial growth factor,VEGF)及神经轴突导向因子-1(neuron towards axon guidance factor-1,netrin-1)水平表达及 Furin 基因 P1 启动区 r2071410 C/T 位点多态性,探讨其与深圳地区EMT发病的相关性.方法 选取2021年5月~2023年1月深圳市龙华区人民医院确诊的EMT患者102例为EMT组,并根据r-AFs分期法将EMT组分为Ⅰ~Ⅱ期和Ⅲ~Ⅳ期.同时收集同期非EMT患者78例为对照组.采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清 Furin,TGF-β,VEGF 及 netrin-1 水平,并采用反转录-实时荧光定量聚合酶链反应法(reverse transcription-real time quantitative polymerase chain reaction,RT-qPCR)分析Furin基因P1启动区r2071410 C/T位点多态性.结果 EMT组患者血清Furin(140.84±47.02pg/ml),TGF-β(376.46±82.36ng/L)和 VEGF 水平(167.67±53.02ng/L)明显高于对照组(55.49±13.67pg/ml,216.37±15.04ng/L,102.27±8.45ng/L),而 netrin-1 水平(48.37±15.20pg/ml)明显低于对照组(165.85±15.63pg/ml),差异具有统计学意义(t=28.409,20.347,16.915,36.653,均 P<0.05).Ⅲ~Ⅳ 期患者血清 Furin(192.41±20.62pg/ml),TGF-β(452.61±72.03ng/L)和 VEGF 水平(201.84±28.01ng/L)明显高于 Ⅰ~Ⅱ 期(78.05±16.54pg/ml,283.75±56.92ng/L,126.07±19.35ng/L),而 netrin-1 水平(37.95±11.34pg/ml)明显低于 Ⅰ~Ⅱ 期(61.05±9.52pg/ml),差异有统计学意义(t=31.071,18.054,19.183,21.625,均 P<0.05).经 Pearson/Spearman 相关性分析结果显示,Furin 与 TGF-β,VEGF水平及临床分期呈正相关(r=0.614 9,0.752 6,0.790 5,均P<0.05),而与netrin-1水平呈负相关(r=-0.670 1,均P<0.05).EMT组患者Furin基因P1启动区r2071410 C/T位点TT基因型和T等位基因频率(42.16%,55.39%)明显高于对照组(7.69%,19.87%),且Ⅲ~Ⅳ期TT基因型和T等位基因频率(51.79%,65.18%)比Ⅰ~Ⅱ期(30.43%,43.48%)明显升高,差异具有统计学意义(x2=26.500,46.472,4.721,9.626,均P<0.05).EMT组不同基因型患者血清Furin水平差异具有统计学意义(F=51.286,P<0.001),其中TT基因型患者血清Furin水平(216.29±68.53pg/ml)明显高于CC(83.04±21.37pg/ml)和CT基因型(89.18±20.95pg/ml),差异具有统计学意义(t=27.146,25.719,均P<0.01),但CC与CT基因型之间差异无统计学意义(t=1.326,P>0.05).结论 EMT患者血清Furin水平明显升高,且与TGF-β,VEGF,netrin-1水平及临床分期呈一定相关性;同时Furin基因P1启动区r2071410 C/T位点呈多态性分布,其中TT基因型患者血清Furin水平升高更为明显,可能与深圳地区EMT发病有关.
Analysis of Serum Furin,TGF-β,VEGF and netrin-1 Levels Expression and Polymorphism of r2071410 C/T Locus in the Furin Gene P1 Promoter Region in Patients with Different r-AFS Stages of Endometriosis
Objective To investigate Furin,tumor growth factor-β(TGF-β),vascular endothelial growth factor(VEGF),neuron towards axon guidance factor-1(netrin-1)level expressions and polymorphism of Furin gene P1 promoter r2071410 locus C/T in endometriosis(EMT)patients with different r-AFS stages,and explore the correlation with the incidence of EMT in Shenzhen.Methods A total of 102 patients diagnosed with EMT from May 2021 to January 2023 in the People's Hospital of Longhua,Shenzhen were selected as EMT group,and the EMT group was divided into stage Ⅰ to Ⅱ group and stageⅢ to Ⅳ group according to r-AFS staging method.At the same time,78 non-EMT patients were collected as control group.The levels of serum Furin,TGF-β,VEGF and netrin-1 were detected by enzyme-linked immunosorbent assay(ELISA),and the polymorphism of the r2071410 C/T locus in the P1 promoter region of Furin gene was analyzed by reverse transcription-real time quantitative polymerase chain reaction(RT-qPCR).Results The levels of Furin(140.84±47.02pg/ml),TGF-β(376.46±82.36ng/L)and VEGF(167.67±53.02ng/L)in EMT group were higher than those in control group(55.49±13.67pg/ml,216.37±15.04ng/L,102.27±8.45ng/L),while the level of netrin-1(48.37±15.20pg/ml)was lower than that of the control group(165.85±15.63pg/ml),with significant differences(t=28.409,20.347,16.915,36.653,all P<0.05).The levels of Furin(192.41±20.62pg/ml),TGF-β(452.61±72.03ng/L)and VEGF(201.84±28.01ng/L)in patients with stage Ⅲ to Ⅳ were higher than those in patients with stage Ⅰ to Ⅱ(78.05±16.54pg/ml,283.75±56.92ng/L,126.07±19.35ng/L),while the level of netrin-1(37.95±11.34pg/ml)was lower than that of stage Ⅰ to Ⅱ(61.05±9.52pg/ml),with significant differences(t=31.071,18.054,19.183,21.625,all P<0.05).Pearson/Spearman correlation analysis showed that Furin was positively correlated with levels of TGF-β and VEGF and clinical stage(r=0.614 9,0.752 6,0.790 5,均 P<0.05),but negatively correlated with netrin-1 level(r=-0.670 1,all P<0.05).The TT genotype and T allele frequencies at r2071410 C/T locus of Furin gene P1 promoter in EMT group(42.16%,55.39%)were higher than those in control group(7.69%,19.87%),while the TT genotype and T allele frequencies at stages Ⅲ to Ⅳ(51.79%,65.18%)were higher than those at stage Ⅰ to Ⅱ(30.43%,43.48%),and the differences were statistically significant(x2=26.500,46.472,4.721,9.626,all P<0.05).The Furin level of patients with different genotypes in EMT group was different(F=51.286,P<0.001),in which the Furin level of TT genotype(216.29±68.53pg/ml)was higher than that of CC(83.04±21.37pg/ml)and CT genotype,(89.18±20.95pg/ml),and the differences were statistically significant(t=27.146,25.719,all P<0.01),but there was no significant difference between CC and CT genotypes(t=1.326,P>0.05).Conclusion The level of Furin in EMT patients was increased,and it was certainly correlated with the levels of TGF-β,VEGF,netrin-1 and clinical stage.Meanwhile,the r2071410 C/T locus in the promoter region of Furin gene P1 showed a polymorphic distribution,in which the Furin level increased more significantly in patients with TT genotype,which may be related to the incidence of EMT in Shenzhen area.

endometriosisFurintumor growth factor-βvascular endothelial growth factorneuron towards axon guidance factor-1Furin gene P1 promotersingle nucleotide polymorphism

鲁鹏、李甜甜、龙诗芬、张燕、季新梅

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深圳市龙华区人民医院妇科,广东 518109

子宫内膜异位症 弗林蛋白酶 肿瘤生长因子-β 血管生长因子 神经轴突导向因子-1 Furin基因P1启动区 单核苷酸多态性

深圳市龙华区医疗卫生机构区级科研资助项目

2021092

2024

现代检验医学杂志
陕西省临床检验中心,陕西省人民医院

现代检验医学杂志

CSTPCD
影响因子:0.713
ISSN:1671-7414
年,卷(期):2024.39(4)