[1]鲁 鹏,李甜甜,龙诗芬,等.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[J].现代检验医学杂志,2024,39(04):23-27+82.[doi:10.3969/j.issn.1671-7414.2024.04.005]
 LU Peng,LI Tiantian,LONG Shifen,et al.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[J].Journal of Modern Laboratory Medicine,2024,39(04):23-27+82.[doi:10.3969/j.issn.1671-7414.2024.04.005]
点击复制

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()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年04期
页码:
23-27+82
栏目:
论著
出版日期:
2024-07-15

文章信息/Info

Title:
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
文章编号:
1671-7414(2024)04-023-06
作者:
鲁 鹏李甜甜龙诗芬张 燕季新梅
(深圳市龙华区人民医院妇科,广东 518109)
Author(s):
LU Peng LI Tiantian LONG Shifen ZHANG Yan JI Xinmei
(Department of Gynecology, the People’s Hospital of Longhua,Shenzhen, Guangdong Shenzhen 518109, China)
关键词:
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-1Furin基因P1 启动区单核苷酸多态性
分类号:
R714.2;R392.11
DOI:
10.3969/j.issn.1671-7414.2024.04.005
文献标志码:
A
摘要:
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(χ2=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。
Abstract:
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 stage III 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 (χ2=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.

参考文献/References:

[1] 王之丰, 周洋, 丁怡娜, 等. 外周血炎症因子、凝血指标在评估子宫内膜异位症患者盆腔粘连中的价值[J]. 检验医学, 2021, 36(10):1050-1054. WANG Zhifeng, ZHOU Yang, DING Yina, et al. Roles of peripheral blood inflammatory factors and coagulation indicators in endometriosis patients with pelvic adhesion[J]. Laboratory Medicine, 2021, 36(10): 1050-1054.
[2] 王迎瑶, 陈友国. 子宫内膜异位症所致不孕的免疫学研究进展[J]. 大连医科大学学报, 2022, 44(4):362-365, 369. WANG Yingyao, CHEN Youguo. Advances in immunology on infertility associated with endometriosis[J]. Journal of Dalian Medical University, 2022, 44(4): 362-365, 369.
[3] 宋方茗, 高一洁, 刘志娟, 等. 弗林蛋白酶的研究进展[J]. 广西医科大学学报, 2021, 38(12): 2372-2379. SONG Fangming, GAO Yijie, LIU Zhijuan, et al. Recent advance of member of proprotein convertases: Furin[J]. Journal of Guangxi Medical University, 2021, 38(12): 2372-2379.
[4] HE Zongsheng, KHATIB A M, CREEMERS J W M. Loss of proprotein convertase furin in mammary gland impairs proIGF1R and proIR processing and suppresses tumorigenesis in triple negative breast cancer[J]. Cancers, 2020, 12(9): 2686.
[5] 刘铁红, 董琳琳, 高阿妮, 等. 血清Furin, Nesfatin-1水平与急性ST 段抬高型心肌梗死预后的关系[J].东南大学学报( 医学版), 2022, 41(2): 260-265. LIU Tiehong, DONG Linlin, GAO Ani, et al. Relationship between serum Furin, Nesfatin-1 and prognosis of patients with acute ST-segment elevation myocardial infarction[J]. Journal of Southeast University (Medical Science Edition), 2022, 41(2): 260-265.
[6] 迪丽尼格尔·吐尔逊, 李南方. 维吾尔族胰岛素抵抗与Furin 基因多态性相关性的研究[J]. 中国糖尿病杂志, 2023, 31(4): 251-254. DILNIGAR Tursun, LI Nanfang. Association between insulin resistance and Furin gene polymorphism in Uighur[J]. Chinese Journal of Diabetes, 2023, 31(4): 251-254.
[7] 丁屹, 袁霞, 顾文文, 等. 子宫内膜异位患者TGF-β,VEGF 和ICAM-1 水平及与临床分期关系[J]. 中国计划生育学杂志, 2020, 28(4): 543-545. DING Yi, YUAN Xia, GU Wenwen, et al. The relationship between the levels of TGF-β, VEGF and ICAM-1 of women with endometriosis and their clinical staging of endometriosis[J]. Chinese Journal of Family Planning, 2020, 28(4): 543-545.
[8] 孙丹, 曹锐, 王化丽, 等. 子宫内膜异位症患者血清nesfatin-1, netrin-1 表达水平及与临床症状关系[J].中国计划生育学杂志, 2022, 30(8): 1901-1904, 1907. SUN Dan, CAO Rui, WANG Huali, et al. Serum feeding inhibitor-1 and neural axon guidance factor-1 expression levels of women with endometriosis and their correlation with the clinical symptoms[J]. Chinese Journal of Family Planning, 2022, 30(8): 1901-1904, 1907.
[9] 中国医师协会妇产科医师分会,中华医学会妇产科学分会子宫内膜异位症协作组. 子宫内膜异位症诊治指南( 第三版)[J]. 中华妇产科杂志, 2021, 56(12):812-824. Chinese Obstetricians and Gynecologists Association, Cooperative Group of Endometriosis, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. Guideline for the diagnosis and treatment of endometriosis(third edition)[J]. Chinese Journal of Obstetrics and Gynecology, 2021, 56(12): 812-824.
[10] 孙梦祝, 黄文庆. 子宫内膜异位症的发病机制与临床诊疗研究进展[J]. 国际检验医学杂志, 2023,44(16): 2017-2022. SUN Mengzhu, HUANG Wenqing. Research advances on pathogenesis and clinical diagnosis and treatment of endometriosis[J]. International Journal of Laboratory Medicine, 2023, 44(16): 2017-2022.
[11] 张阳, 丁玲玲, 项兰兰. 子宫内膜异位症合并不孕症女性PAI-1,HOXA10 基因表达及其临床意义[J]. 中国计划生育学杂志, 2022, 30(11): 2575-2578. ZHANG Yang, DING Lingling, XIANG Lanlan. Expressions of PAI-1 and HOXA10 genes and their clinical significances of infertility women with endometriosis[J]. Chinese Journal of Family Planning, 2022, 30(11): 2575-2578.
[12] 陈亚慧, 王亚楠, 王琳, 等. 501 例腹壁子宫内膜异位症相关临床因素分析[J]. 现代妇产科进展, 2023,32(10): 768-771, 775. CHEN Yahui, WANG Yanan, WANG Lin, et al. Analysis of clinical factors related to 501 cases abdominal endometriosis[J]. Progress in Obstetrics and Gynecology, 2023, 32(10): 768-771, 775.
[13] 司胜勇, 李治菁, 缪思斯, 等.LncRNA MIR155HG通过调控miR-133a-3p/Furin 轴对心肌成纤维细胞增殖、迁移、分化和胶原合成的影响[J]. 中国动脉硬化杂志, 2020, 28(12): 1026-1033, 1059. SI Shengyong, LI Zhijing, MIU Sisi, et al. Effects of lncRNA MIR155HG on proliferation, migration, differentiation and collagen synthesis of myocardial fibroblasts by regulating miR-133a-3p/Furin axis[J]. Chinese Journal of Arteriosclerosis, 2020, 28(12):1026-1033, 1059.
[14] 岳晓琳, 米晓燕, 白圆圆, 等. 原发性舍格伦综合征患者血浆弗林蛋白酶和Th1 型细胞因子水平表达与唇腺损害及相关腺体功能的关系研究[J]. 现代检验医学杂志, 2021, 36(4): 10-14, 50. YUE Xiaolin, MI Xiaoyan, BAI Yuanyuan, et al. Relationship between plasma FURIN and Th1 type cytokines level, labial gland damage and related glandular function in patients with primary Sjogren’s syndrome[J]. Journal of Modern Laboratory Medicine, 2021, 36(4): 10-14, 50.
[15] KOCYIGIT A, SOGUT O, DURMUS E, et al. Circulating furin, IL-6, and presepsin levels and disease severity in SARS-CoV-2-infected patients[J]. Science Progress, 2021, 104(suppl 2): 368504211026119.
[16] 张华文, 杨立, 任琛琛, 等. 脂联素基因多态性与子宫内膜异位症的相关性[J]. 现代妇产科进展, 2021,30(4): 259-263, 269. ZHANG Huawen, YANG Li, REN Chenchen, et al. Role of adiponectin gene polymorphisms in endometriosis[J]. Progress in Obstetrics and Gynecology, 2021, 30(4): 259-263, 269.
[17] 曾辉苑, 张燕, 刘国栋, 等. 子宫内膜异位症患者血清中PAPP-A,IGF-I 水平及PAPP-A 基因rs7020782A/C 位点多态性与临床分期相关性研究[J]. 现代检验医学杂志, 2022, 37(1): 33-37. ZENG Huiyuan, ZHANG Yan, LIU Guodong, et al. Study on the correlation between the levels of PAPP-A, IGF-I and PAPP-A gene rs7020782 A/C loci polymorphism and clinical stage in patients with endometriosis[J]. Journal of Modern Laboratory Medicine, 2022, 37(1): 33-37.
[18] 王玉凤, 毛婷. CYP1B1 基因RS1800440A/G 与RS1056836 C/G 联合基因型多态性与子宫内膜异位症易感性的相关性[J]. 吉林医学, 2023, 44(8): 2092-2095. WANG Yufeng, MAO Ting. Relationship between endometriosis and combined polymorphisms of CYP1B1 RS1800440 A/G and CYP1B1 RS1056836 C/G[J]. Jilin Medical Journal, 2023, 44(8): 2092-2095.
[19] 任丽云. Furin 蛋白及其编码基因启动子区域DNA甲基化与高血压关系的前瞻性队列研究[D]. 苏州:苏州大学, 2021. REN Liyun. Prospective cohort study on the relationship between DNA methylation in the promoter region of furin protein and its coding gene and hypertension[D]. Suzhou: Suzhou University, 2021.
[20] 李艳, 王静, 袁琛, 等. Furin 基因对高血压心肌梗死细胞增殖、迁移以及作用机制的研究[J]. 临床和实验医学杂志, 2018, 17(9): 913-916. LI Yan, WANG Jing, YUAN Chen, et al. The study of Furin gene on the proliferation, migration and mechanism of hypertensive myocardial infarction cells[J]. Journal of Clinical and Experimental Medicine, 2018, 17(9): 913-916.

相似文献/References:

[1]鲁晓燕a,刘曼华a,赵 枰b,等.紧密连接蛋白Claudin-4在子宫内膜异位症组织中的表达[J].现代检验医学杂志,2016,31(04):62.[doi:10.3969/j.issn.16717-414.2016.04.016]
 LU Xiao-yana,LIU Man-huaa,ZHAO Pingb,et al.Expressions of Claudin-4 mRNA in Endometriosis[J].Journal of Modern Laboratory Medicine,2016,31(04):62.[doi:10.3969/j.issn.16717-414.2016.04.016]
[2]丁亚丽.子宫内膜异位综合征患者血清 AMH和 IGF-1水平表达对不孕症术后妊娠的影响[J].现代检验医学杂志,2021,36(01):120.[doi:10.3969/j.issn.1671-7414.2021.01.030]
 DING Ya-li.Effect of Serum AMH and IGF-1 Expression Levels on Postoperative Pregnancy in Infertility Patients with Endometriosis Syndrome[J].Journal of Modern Laboratory Medicine,2021,36(04):120.[doi:10.3969/j.issn.1671-7414.2021.01.030]
[3]岳晓琳,米晓燕,白圆圆,等.原发性舍格伦综合征患者血浆弗林蛋白酶和Th1型细胞因子水平表达与唇腺损害及相关腺体功能的关系研究[J].现代检验医学杂志,2021,36(04):10.[doi:10.3969/j.issn.1671-7414.2021.04.003]
 YUE Xiao-lin,MI Xiao-yan,Bai Yuan-yuan,et al.Relationship between Plasma FURIN and Th1 Type Cytokines Level, LabialGland Damage and Related Glandular Function in Patients with PrimarySjogren’s Syndrome[J].Journal of Modern Laboratory Medicine,2021,36(04):10.[doi:10.3969/j.issn.1671-7414.2021.04.003]
[4]曾辉苑a,张 燕a,刘国栋b,等.子宫内膜异位症患者血清中 PAPP-A,IGF-I水平及 PAPP-A基因 rs7020782 A/C位点多态性与临床分期相关性研究[J].现代检验医学杂志,2022,37(01):33.[doi:10.3969/j.issn.1671-7414.2022.01.007]
 ZENG Hui-yuana,ZHANG Yana,LIU Guo-dongb,et al.Study on the Correlation between the Levels of PAPP-A,IGF-I and PAPP-A Gene rs7020782 A/C Loci Polymorphism andClinical Stage in Patients with Endometriosis[J].Journal of Modern Laboratory Medicine,2022,37(04):33.[doi:10.3969/j.issn.1671-7414.2022.01.007]
[5]张 璇,赵爱琴,邹 丹,等.子宫内膜异位症患者血清miR-455 和FABP4 表达水平及临床意义[J].现代检验医学杂志,2022,37(04):49.[doi:10.3969/j.issn.1671-7414.2022.04.010]
 ZHANG Xuan,ZHAO Ai-qin,ZOU Dan,et al.Expression Level and Clinical Significance of Serum miR-455 and FABP4 in Patients with Endometriosis[J].Journal of Modern Laboratory Medicine,2022,37(04):49.[doi:10.3969/j.issn.1671-7414.2022.04.010]
[6]孙晓华,宋雨霖,李 红.子宫内膜异位症患者血清VEGFR-1 和MIP-3α 水平表达对术后复发的预测价值研究[J].现代检验医学杂志,2024,39(04):170.[doi:10.3969/j.issn.1671-7414.2024.04.031]
 SUN Xiaohua,SONG Yulin,LI Hong.Study on the Predictive Value of Serum VEGFR-1 and MIP-3α Level Expression in Endometriosis Patients on Postoperative Recurrence[J].Journal of Modern Laboratory Medicine,2024,39(04):170.[doi:10.3969/j.issn.1671-7414.2024.04.031]

备注/Memo

备注/Memo:
基金项目:深圳市龙华区医疗卫生机构区级科研资助项目(编号:2021092)。
作者简介:鲁鹏(1997-),女,硕士,医师,主要从事临床妇科疾病的诊疗工作,E-mail: 18824679562@163.com。
通讯作者:季新梅(1966-),女,主任医师,专业:妇科,E-mail: 15764504086@163.com。
更新日期/Last Update: 2024-07-15