Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Human ciliary muscle cell responses to kinins:Activation of ERK1/2 and pro-matrix metalloproteinases secretion

AIM To study activation of extracellular signal-regulated kinase-1/2(ERK1/2) and pro-matrix metalloproteinases(pro-MMPs) secretion from isolated primary human ciliary muscle(h-CM) cells in response to bradykinin(BK) and other agonists. METHODS Serum-starved h-CM cells were challenged with vehicle, BK agonists or antagonists. Cell lysates were evaluated for phosphorylated ERK1/2 using homogeneous timeresolved fluorescence technology based on a sandwich immunoassay. Rabbit polyclonal anti-pro-MMP antibodies were used to measure pro-MMPs using immunoblot analysis.RESULTS A 10 min incubation time using 5 × 104 h-CM cells/well was optimum condition for studying stimulation of ERK1/2 phosphorylation. BK(100 nmol/L) caused a 1.86 ± 0.26 fold(n = 3) increase in ERK1/2 phosphorylation above baseline. BK analogs, Met-Lys-BK and RMP-7(100 nmol/L), also stimulated ERK1/2 phosphorylation by 1.57 ± 0.04 and 1.55 ± 0.09 fold, respectively. However, DesArg9-Bradykinin, a B1 receptor-selective agonist(0.1-1 μmol/L), was essentially inactive. HOE-140 or WIN-64338(B2-antagonists) appreciably blocked phosphorylation of ERK1/2 induced by various BK agonists. Pre-treatmentof cells with a prostaglandin(PG) synthase inhibitor(bromfenac; 1 μmol/L) failed to alter kinin-induced ERK1/2 activation. BK and a non-peptide BK agonist(FR-190997)(10 nmol/L-1 μmol/L) also enhanced pro-MMPs secretion(pro-MMP-1 > pro-MMP-3 > pro-MMP-2; 1.45-1.75-fold over baseline) from h-CM cells. CONCLUSION These collective data suggest that B2 kinin receptors initiate signaling in h-CM cells by a relatively rapid mechanism(within minutes) involving ERK1/2 activation which in turn regulates MMPs production(within hours). The latter process does not involve PGs.

Correlation of matrix metalloproteinase－2, －9, tissue inhibitor－1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase 2, 9 (MMP 2, MMP 9), tissue inhibitor 1 of matrix metalloproteinase (TIMP 1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP 2, MMP 9, TIMP 1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship ( P <0.05) between the expression of MMP 2 and MMP 9, TIMP 1 and CD44v6, HER2/neu and MMP 9, MMP 2 and p53. Up regulation of MMP 2 was accompanied by advanced T stage ( P <0.01) . There was also a trend of MMP 2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence( P <0.05). The expression of TIMP 1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non keratinizing SCC than that in basaloid SCC( P <0.05). These findings suggested that MMP 2 and MMP 9, HER2/neu and MMP 9, MMP 2 and p53 had a coordinate function in aggression of tumor; that MMP 2 had a more important function than MMP 9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.

Do different bariatric surgical procedures influence plasma levels of matrix metalloproteinase-2,-7,and-9 among patients with type 2 diabetes mellitus?

BACKGROUND Bariatric surgery is an efficient strategy for body weight and type 2 diabetes mellitus(T2 DM) management. Abnormal lipid deposition in visceral organs,especially the pancreas and liver, might cause beta-cell dysfunction and insulin resistance. Extracellular matrix(ECM) remodeling allows adipose expansion, and matrix metalloproteinases(MMPs) play essential roles in ECM construction.MMP-2 and MMP-9 are the substrates of MMP-7. Different studies have reported that MMP-2,-7, and-9 increase in patients with obesity and metabolic syndromes or T2 DM and are considered biomarkers in obesity and hyperglycemia patients.AIMTo prospectively investigate whether MMP-2, MMP-7, and MMP-9 differ after two bariatric surgeries: Gastric bypass(GB) and sleeve gastrectomy(SG).METHODS We performed GB in 23 and SG in 19 obese patients with T2 DM. We measured body weight, waist circumference, body mass index(BMI), and serum concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood sugar(FBS),hemoglobin A1 c(Hb A1 c), C-peptide, homeostasis model assessments of insulin resistance, and MMP-2, MMP-7, and MMP-9 levels at baseline and at 3, 12, and 24 mo post-operation.RESULTS Twenty-three patients aged 44.7 ± 9.7 years underwent GB, and 19 patients aged40.1 ± 9.1 years underwent SG. In the GB group, BMI decreased from 30.3 ± 3.4 to24.4 ± 2.4 kg/m2, Hb A1 c decreased from 9.2% ± 1.5% to 6.7% ± 1.4%, and FBS decreased from 171.6 ± 65.0 mg/d L to 117.7 ± 37.5 mg/d L 2 years post-operation(P < 0.001). However, the MMP-2, MMP-7, and MMP-9 levels pre-and post-GB were similar even 2 years post-operation(P = 0.107, 0.258, and 0.466,respectively). The SG group revealed similar results: BMI decreased from 36.2 ±5.1 to 26.9 ± 4.7 kg/m2, Hb A1 c decreased from 7.9% ± 1.7% to 5.8% ± 0.6%, and FBS decreased from 138.3 ± 55.6 mg/d L to 95.1 ± 3.1 mg/d L(P < 0.001). The serum MMP-2,-7, and-9 levels pre-and post-SG were not different(P = 0.083,0.869, and 0.1, respectively).CONCLUSION Improvements in obesity and T2 DM induced by bariatric surgery might be the result of MMP-2,-7, or-9 independent pathways.

Time dependent integration of matrix metalloproteinases and their targeted substrates directs axonal sprouting and synaptogenesis following central nervous system injury

Over the past two decades, many investigators have reported how extracellular matrix molecules act to regulate neuroplasticity. The majority of these studies involve proteins which are targets of matrix metalloproteinases. Importantly, these enzyme/substrate interactions can regulate degenerative and regenerative phases of synaptic plasticity, directing axonal and dendritic reorganization after brain insult. The present review first summarizes literature support for the prominent role of matrix metalloproteinases during neuroregeneration, followed by a discussion of data contrasting adaptive and maladaptive neuroplasticity that reveals time-dependent metalloproteinase/substrate regulation of postinjury synaptic recovery. The potential for these enzymes to serve as therapeutic targets for enhanced neuroplasticity after brain injury is illustrated with experiments demonstrating that metalloproteinase inhibitors can alter adaptive and maladaptive outcome. Finally, the complexity of metalloproteinase role in reactive synaptogenesis is revealed in new studies showing how these enzymes interact with immune molecules to mediate cellular response in the local regenerative environment, and are regulated by novel binding partners in the brain extracellular matrix. Together, these different examples show the complexity with which metalloproteinases are integrated into the process of neuroregeneration, and point to a promising new angle for future studies exploring how to facilitate brain plasticity.

Correlation of RECK with Matrix Metalloproteinase-2 in Regulation of Trophoblast Invasion of Early Pregnancy

To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs （RECK） gene and matrix metalloproteinase-2 （MMP-2） in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women （27 in the early pregnancy, 25 in the term pregnancy）. Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group （P〈0.05）. RECK expression was significantly lower in cellular column （CC） with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy （P〈0.05）. The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35±0.14 and 2.68±0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time （P〈0.01）. The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46±0.05 and 0.10±0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy.

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China

Matrix metalloproteinase 2(MMP2) has been shown to play an important role in several steps of cancer development.The-1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele,and the CC genotype in the MMP2 promoter has been reported to associate with the development of several cancers.To assess the contribution of the MMP2-1306C/T polymorphism to the risk of nasopharyngeal carcinoma(NPC),we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele analysis.We found that subjects with the CC genotype had an increased risk(OR = 1.55,95% CI = 1.05-2.27) of developing NPC compared to those with the CT or TT genotypes.Furthermore,we found that the risk of NPC was markedly increased in subjects who were smokers(OR = 15.04,95% CI = 6.65-33.99),heavy smokers who smoked ≥20 pack-years(OR = 18.66,95% CI = 7.67-45.38),or young(<60 years) at diagnosis(OR = 1.52,95% CI = 1.01-2.29).Our results provide molecular epidemiological evidence that the MMP2-1306C/T promoter polymorphism is associated with NPC risk,and this association is especially noteworthy in heavy smokers.

Distribution and relative activity of matrix metalloproteinase-2 in human coronal dentin

The presence of matrix metalloproteinase-2 （MMP-2） in dentin has been reported, but its distribution and activity level in mature human coronal dentin are not well understood. The purpose of this study was to determine the MMP-2 distribution and relative activity in demineralized dentin. Crowns of twenty eight human molars were sectioned into inner （ID）, middle （MD）, and outer dentin （OD） regions and demineralized. MMP-2 was extracted with 0.33 mol·L-1 EDTA/2 mol·L-1 guanidine-HCl, pH 7.4, and MMP-2 concentration was estimated with enzyme-linked immunoabsorbant assay （ELISA）. Further characterization was accomplished by Western blotting analysis and gelatin zymography. The mean concentrations of MMP-2 per mg dentin protein in the dentin regions were significantly different （P=0.043）： 0.9 ng （ID）, 0.4 ng （MD）, and 2.2 ng （OD）, respectively. The pattern of MMP-2 concentration was OD〉ID〉MD. Western blotting analysis detected -66 and -72 kDa immunopositive proteins corresponding to pro- and mature MMP-2, respectively, in the ID and MD, and a -66 kDa protein in the OD. Gelatinolytic activity consistent with MMP-2 was detected in all regions. Interestingly, the pattern of levels of Western blot immunodetection and gelatinolytic activity was MD〉ID〉OD. The eoneentration of MMP-2 in human coronal dentin was highest in the region of dentin that contains the dentinoenamel junction and least in the middle region of dentin. However, levels of Western blot immunodetection and gelatinolytic activity did not correlate with the estimated regional concentrations of MMP-2, potentially indicating region specific protein interactions.

Vascular Endothelial Growth Factorl65-regulated Nasopharyngeal Carcinoma Cell Lines Invasion and Migration Involve Expression and Activation of Matrix Metalloproteinase-2

The effect of vascular endothelial growth factor （VEGF） overexpression on matrix metalloproteinase-2 （MMP-2） in nasopharyngeal carcinoma （NPC） cells in vitro and the possible mechanism involved were investigated, and the correlation between the expression of VEGF and MMP-2 in NPC evaluated. The NPC cells were transfected with PAd-trackVEGF165 plasmid. The expression levels of VEGF and MMP-2 mRNA and protein in NPC cells were detected by semi-quantitative RT-PCR and Western blot respectively. It was found that the expression of VEGF and MMP-2 mRNA and protein was significantly increased in NPC cells after transfection of VEGF 165. It was concluded that the expression of VEGF was correlated to the in vitro invasion of NPC cells, and the induction of MMP-2 by VEGF was a key process of NPC cell invasion.

Immunohistochemical Studies of the Expression of Matrix Metalloproteinase-2 and Metalloproteinase-9 in Human Prostate Cancer

To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hyperplasia (BPH). Our results showed that matrix metalloproteinase 2 and 9 levels in prostate cancer were much higher than those in tissues of BPH, with the cancer invasion being positively correlated with the expression of the metalloproteinases. It is concluded that matrix metalloproteinase 2 and 9 are better molecular markers, which are of help in the diagnosis and prediction of prognosis of prostate cancer.

EXPRESSION OF MATRIX METALLOPROTEINASE-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN HUMAN GLIOMA AND THEIR RELATION TO THE INVASION OF THE TUMOR

Objective To study the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in different grade human glioma. To investigate their relation to the pathological grade and invasion of the tumor. Methods The expression of MMP-2 and VEGF were determined by immunohistochemical technique in 48 cases of human glioma and 10 specimens of normal brain tissue. Results The expression levels of MMP-2 and VEGF in human glioma were positively related to tumor grades (P<0.01), and their expressions in the glioma of grade Ⅲ and Ⅳ were significantly different from those in the glioma of grade Ⅰ-Ⅱand normal brain tissue (P<0.01). The expression of MMP-2 was positively correlated to that of VEGF (P<0.01). Conclusion MMP-2 and VEGF were highly expression in human glioma and were positively related to the tumor grades. The synergic interaction of MMP-2 and VEGF promoted the angiogenesis and invasion of human glioma.

替吉奥联合奥沙利铂对老年胃癌患者胃动力相关激素及基质金属蛋白酶-2、基质金属蛋白酶-9的影响

目的探讨替吉奥联合奥沙利铂对老年胃癌患者胃动力相关激素及基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)的影响。方法选取128例老年胃癌患者为研究对象,随机分成对照组(n=64)与观察组(n=64)。对照组给予替吉奥治疗,观察组给予替吉奥联合奥沙利铂治疗。观察2组的胃动力相关激素[胃动素(MTL)、血管活性肠肽(VIP)]、MMP-2与MMP-9、肿瘤标志物[癌胚抗原(CEA)、糖类抗原125(CA125)、糖类抗原19-9(CA19-9)]、临床疗效以及不良反应发生情况。分析胃动力相关激素与MMP-2、MMP-9及肿瘤标记物水平的相关性。结果治疗后,2组MTL低于治疗前,VIP高于治疗前,且观察组MTL低于对照组,VIP高于对照组,差异有统计学意义(P<0.05)。治疗后,2组MMP-2、MMP-9及CEA、CA125、CA19-9低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。观察组总有效率为70.31%,高于对照组的53.13%,差异有统计学意义(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。MTL与MMP-2、MMP-9、CEA、CA125、CA19-9呈负相关(P<0.05);VIP与MMP-2、MMP-9、CEA、CA125、CA19-9呈正相关(P<0.05)。结论替吉奥联合奥沙利铂治疗老年胃癌患者的效果较好,且安全性较高。MTL、VIP与MMP-2、MMP-9及CEA、CA125、CA19-9在老年胃癌患者的疾病发展中起相互关联作用。

白内障合并2型糖尿病患者血清ES、MMP-2、MMP-9的表达及其影响因素分析

目的:探讨白内障合并2型糖尿病患者血清血管内皮抑制素(ES)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)的表达及其影响因素。方法:选取2019年1月—2023年1月在昌邑市人民医院就诊的白内障患者90例作为研究对象,将白内障合并2型糖尿病患者48例作为试验组,白内障未合并2型糖尿病患者42例作为对照组。两组均检测血清血糖、ES、MMP-2、MMP-9水平,分析白内障合并2型糖尿病患者ES、MMP-2、MMP-9高表达的影响因素,分析白内障合并2型糖尿病患者ES水平与MMP-2、MMP-9、血糖的相关性。结果:与对照组比较,试验组空腹血糖、ES、MMP-2、MMP-9水平明显更高(P<0.05)。空腹血糖浓度是白内障合并2型糖尿病患者ES、MMP-2、MMP-9高表达的影响因素(P<0.05)。白内障合并2型糖尿病患者ES水平与MMP-2、MMP-9、空腹血糖浓度呈正相关(P<0.05)。结论:白内障合并2型糖尿病患者血清ES、MMP-2、MMP-9表达水平较高,与空腹血糖浓度有关,且血清ES水平与MMP-2、MMP-9、空腹血糖浓度呈正相关。

EGR-1和MMP-2在早期自然流产患者中的表达及临床意义

目的探讨早期生长反应因子(EGR-1)和基质金属蛋白酶-2(MMP-2)在早期自然流产患者绒毛中的表达及临床意义。方法采用RT-PCR和Westernblot检测20例早期自然流产患者(流产组)和20例正常早孕人工流产(对照组)绒毛组织中EGR-1和MMP-2的表达情况。结果流产组中EGR-1、MMP-2 mRNA和蛋白水平明显低于对照组,差异有统计学意义(P<0.05)。结论EGR-1和MMP-2在早孕绒毛组织中表达异常可能参与早期妊娠失败的发生。

寻常型银屑病患者血清脂质运载蛋白2、基质金属蛋白酶9水平与病情及预后的相关性分析

目的探讨寻常型银屑病(PV)患者血清脂质运载蛋白2(LCN2)、基质金属蛋白酶9(MMP9)水平与病情严重程度及预后的相关性。方法选取2021年1月至2022年2月于延安大学附属医院就诊的88例PV患者作为研究组,采用银屑病皮肤面积和严重指数(PASI)评分对PV患者病情进行评估,根据病情分为轻度组(n=46)、中度组(n=31)、重度组(n=11),根据治疗后6个月内的皮损消退程度分为预后良好组(n=67)、预后不良组(n=21),另选取同期于延安大学附属医院体检的年龄、性别、体重指数与研究组相匹配的健康人群88例为对照组。采用Spearman法分析PV患者PASI评分与血清LCN2、MMP9水平的相关性,采用受试者操作特征(ROC)曲线分析血清LCN2、MMP9预测PV患者预后的临床效能。结果研究组与对照组的年龄、性别、体重指数、吸烟史占比、饮酒史占比方面比较差异均无统计学意义(P>0.05)。研究组血清LCN2、MMP9水平高于对照组,差异均有统计学意义(P<0.05)。重度组患者血清LCN2、MMP9水平高于中度组和轻度组,中度组患者血清LCN2、MMP9水平高于轻度组,差异均有统计学意义(P<0.05)。经Spearman法分析结果显示,PV患者PASI评分与血清LCN2、MMP9水平均呈正相关(r=0.666、0.518,P<0.05)。预后不良组患者血清LCN2、MMP9水平均高于预后良好组,差异有统计学意义(P<0.05)。ROC曲线分析结果显示,血清LCN2、MMP9联合检测对PV患者预后的预测效能优于二者单独检测(P<0.05)。结论PV患者血清LCN2、MMP9表达水平与病情严重程度密切相关,二者联合检测对PV患者的预后状态具有较高的预测效能。

子宫肌瘤组织中MMP-2、MLCK、VEGF及IGF-2表达及其临床意义

目的分析基质金属蛋白酶-2(MMP-2)、肌球蛋白轻链激酶(MLCK)、血管内皮生长因子(VEGF)、胰岛素样生长因子-2(IGF-2)在子宫肌瘤组织内的表达及临床意义。方法选取76例子宫肌瘤患者,收集其子宫肌瘤组织及正常子宫组织,采用免疫组织化学法测定MMP-2、MLCK、VEGF及IGF-2表达,统计对比两者的阳性率。结果子宫肌瘤组织中MMP-2、MLCK、VEGF及IGF-2阳性表达率分别为69.74%(53/76)、60.53%(46/76)、81.58%(62/76)、92.11%(70/76),高于正常子宫组织的15.79%(12/76)、10.53%(8/76)、17.11%(13/76)、30.26%(23/76),差异有统计学意义(P<0.05)。结论MMP-2、MLCK、VEGF及IGF-2在子宫肌瘤组织中呈异常的高表达,与疾病的发生与发展存在紧密联系。

输卵管阻塞性不孕患者血清TGF-β1、IL-2、MMP-9水平及临床意义

目的:分析输卵管阻塞性不孕患者血清转化生长因子-β1(TGF-β1)、白细胞介素-2(IL-2)、基质金属蛋白酶-9(MMP-9)水平变化及临床意义。方法:以本院2022年3月-2023年10月诊治的60例输卵管阻塞性不孕患者为病例组,正常妊娠分娩的女性50例为对照组。测定对比两组血清TGF-β1、IL-2、MMP-9水平,Pearson相关性分析血清指标间相关性,受试者工作特征(ROC)曲线分析血清指标诊断不孕效能,logistic多因素回归分析输卵管阻塞性不孕发生影响因素。结果:病例组术前血清TGF-β1(593.79±148.23 ng/L)、IL-2(3.90±0.75 ng/L)、MMP-9(384.88±86.87 ng/ml)水平均高于对照组(239.42±113.37 ng/L、3.09±0.84 ng/L、178.98±80.85 ng/ml),术后血清TGF-β1、IL-2、MMP-9水平较术前均下降,血清TGF-β1与IL-2、MMP-9,及IL-2与MMP-9均呈正相关(均P<0.05)。ROC曲线分析,诊断不孕TGF-β1曲线下面积(AUC)0.941、敏感度88.3%、特异度94.0%,IL-2 AUC 0.778、敏感度66.7%、特异度84.0%,MMP-9 AUC 0.946、敏感度88.3%、特异度86.0%,3指标联合诊断AUC为0.992,敏感度93.3%、特异度100.0%。logistic回归分析,血清TGF-β1、IL-2、MMP-9异常升高是输卵管阻塞性不孕发发生的危险因素(均P<0.05)。结论:输卵管阻塞性不孕患者血清TGF-β1、IL-2、MMP-9水平均高表达,且是不孕发生的危险因素,3者联合检测对输卵管阻塞性不孕有较高诊断价值。

Integrin αvβ6 and matrix metalloproteinase 9 correlate with survival in gastric cancer

AIM: To investigate the expression of integrin αvβ6 and matrix metalloproteinase 9 (MMP-9), their association with prognostic factors and to assess their predictive role in gastric cancer patients.METHODS: Immunohistochemistry was used to determine the expressions of integrin αvβ6 and MMP-9 in 126 specimens from patients with primary gastric carcinoma. Associations between immunohistochemical staining and various clinic pathologic variables of tissue specimens were evaluated by the χ2 test and Fisher’s exact test. Expression correlation of αvβ6 and MMP-9 was assessed using bivariate correlation analysis. The patients were followed-up every 3 mo in the first two years and at least every 6 mo afterwards, with a median follow-up of 56 mo (ranging from 2 mo to 94 mo). Four different combinations of αvβ6 and MMP-9 levels (that is, both markers positive, both markers negative, αvβ6 positive with MMP-9 negative, and αvβ6 negative with MMP-9 positive) were evaluated for their relative effect on survival. The difference in survival curves was evaluated with a log-rank test. Survival analysis was conducted using the Kaplan-Meier survival and Cox proportional hazards model analysis.RESULTS: The expressions of integrin αvβ6 and MMP-9 were investigated in 126 cases, among which 34.92% were positive for αvβ6 expression, and 42.06% for MMP-9 expression. The expression of αvβ6 was associated with Lauren type, differentiation, N stage, and TNM stage (the P values were 0.006, 0.038, 0.016, and 0.002, respectively). While MMP-9 expression was associated with differentiation, T stage, N stage, and TNM stage (the P values were 0.039, 0.014, 0.033, and 0.008, respectively). The positive correlation between αvβ6 and MMP-9 in gastric cancer was confirmed by a correlation analysis. The Kaplan-Meier survival analysis showed that patients with expression of αvβ6 or MMP-9 alone died earlier than those with negative expression and that patients who were both αvβ6 and MMP-9 positive had a shorter overall survival than those with the opposite pattern (both αvβ6 and MMP-9 negative) (P = 0.000). A Cox model indicated that positive expression of αvβ6 and MMP-9, diffuse Lauren type, as well as a senior grade of N stage, M stage, and TNM stage were predictors of a poor prognosis in univariate analysis. Only αvβ6 and MMP-9 retained their significance when adjustments were made for other known prognostic factors in multivariate analysis (RR = 2.632, P = 0.003 and RR = 1.813, P = 0.007).CONCLUSION: The expression of αvβ6 and MMP-9 are closely correlated, and the combinational pattern of αvβ6 and MMP-9 can serve as a more effective prognostic index for gastric cancer patients.