目的探讨幽门螺杆菌(Hp)阳性早期胃癌患者肿瘤组织中转化生长因子-β_(1)(TGF-β_(1))mRNA、金属基质蛋白酶-2(MMP-2)mRNA、青霉素结合蛋白1A(PBP1A)m RNA表达水平与复发的关系,并分析其对复发的预测价值。方法选取2018年3月至2023年7...目的探讨幽门螺杆菌(Hp)阳性早期胃癌患者肿瘤组织中转化生长因子-β_(1)(TGF-β_(1))mRNA、金属基质蛋白酶-2(MMP-2)mRNA、青霉素结合蛋白1A(PBP1A)m RNA表达水平与复发的关系,并分析其对复发的预测价值。方法选取2018年3月至2023年7月南阳市中心医院收治的214例Hp阳性早期胃癌患者进行前瞻性研究,所有患者均行内镜黏膜下剥离术(ESD),采用实时荧光定量聚合酶链反应(qRT-PCR)法检测肿瘤组织、癌旁组织中TGF-β_(1)m RNA、MMP-2 m RNA、PBP1A m RNA表达水平,并分析其与临床病理特征相关性。依据ESD术后是否复发分为复发组、未复发组,采用q RT-PCR法检测两组患者的TGF-β_(1)m RNA、MMP-2 m RNA、PBP1A m RNA表达水平。采用偏相关性分析肿瘤组织中TGF-β_(1)m RNA、MMP-2 m RNA、PBP1A m RNA表达水平与复发的关系。采用受试者工作特征(ROC)曲线分析TGF-β_(1)m RNA、MMP-2 mRNA、PBP1A m RNA表达水平对复发的预测价值。结果肿瘤组织中TGF-β_(1)mRNA、MMP-2 m RNA表达水平分别为1.04±0.26、1.45±0.31,明显高于癌旁组织的0.85±0.14、1.18±0.25,PBP1A m RNA表达水平为0.31±0.10,明显低于癌旁组织的0.43±0.12,差异均有统计学意义(P<0.05);列联相关系数C分析显示,肿瘤组织中TGF-β_(1)mRNA、MMP-2 m RNA表达水平与临床分期、浸润深度、淋巴结转移呈正相关(P<0.05),与分化程度呈负相关(P<0.05),而PBP1A m RNA表达水平与临床分期、浸润深度、淋巴结转移呈负相关(P<0.05),与分化程度呈正相关(P<0.05);复发组患者的TGF-β_(1)mRNA、MMP-2 m RNA表达水平分别为1.31±0.25、1.74±0.31,明显高于未复发组的1.01±0.20、1.42±0.25,PBP1A mRNA表达水平为0.18±0.05,明显低于未复发组的0.32±0.10,差异均有统计学意义(P<0.05);偏相关性分析显示,肿瘤组织中TGF-β_(1)mRNA、MMP-2m RNA、PBP1A m RNA表达水平与复发显著相关(P<0.05);TGF-β_(1)mRNA、MMP-2 mRNA、PBP1A mRNA单项及联合预测复发的曲线下面积(AUC)分别为0.755、0.742、0.795、0.915,敏感度为75.00%、70.00%、75.00%、80.00%,特异度为72.25%、67.54%、76.95%、95.81%,且预测效能显著高于各指标单独预测价值(Z=2.376、2.413、1.997,P=0.018、0.016、0.046)。结论Hp阳性早期胃癌患者肿瘤组织中TGF-β_(1)m RNA、MMP-2 m RNA表达水平升高,PBP1A m RNA表达水平降低,且与临床病理特征、复发密切相关,联合检测其水平对复发具有较高的预测价值。展开更多
Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) superfamily of proteins, circulates in a complex with vitronectin. Furthermore, these two proteins are co-localized in the ...Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) superfamily of proteins, circulates in a complex with vitronectin. Furthermore, these two proteins are co-localized in the extracellular matrix (ECM) in many different pathophysiological conditions. Though PAI-1 is a well-characterized inhibitor of serine proteases, recent emphasis has also focused on its protease-independent functions. Vitronectin, a multi-domain protein that binds a wide variety of ligands and proteins, exists in the circulation in a preferred monomeric state, while in the extracellular matrix it exists as a multimer resulting from an altered conformation. Though the mechanism for the conformational alterations and compartmentalization in tissues is unknown, there are a number of biomolecules including PAI-1 that appear to cause such changes. Experimental analysis has established that PAI-1 induces association of vitronectin to higher-order species in a concentration-dependent fashion [1]. This report extends our investigations into the mechanism of the interaction between vitronectin and PAI-1 to explore the physiological relevance of these higher-order complexes for cellular adhesion and migration. In this study, we evaluate the effects of the pericellular microenvironment on the functions of the multimeric complexes in a variety of relevant biological settings. Our findings underscore the importance of the variability of components within this microenvironment, including different receptors and ECM components, in governing the way in which the vitronectin/PAI-1 complex mediates cell-matrix interactions.展开更多
文摘目的探讨幽门螺杆菌(Hp)阳性早期胃癌患者肿瘤组织中转化生长因子-β_(1)(TGF-β_(1))mRNA、金属基质蛋白酶-2(MMP-2)mRNA、青霉素结合蛋白1A(PBP1A)m RNA表达水平与复发的关系,并分析其对复发的预测价值。方法选取2018年3月至2023年7月南阳市中心医院收治的214例Hp阳性早期胃癌患者进行前瞻性研究,所有患者均行内镜黏膜下剥离术(ESD),采用实时荧光定量聚合酶链反应(qRT-PCR)法检测肿瘤组织、癌旁组织中TGF-β_(1)m RNA、MMP-2 m RNA、PBP1A m RNA表达水平,并分析其与临床病理特征相关性。依据ESD术后是否复发分为复发组、未复发组,采用q RT-PCR法检测两组患者的TGF-β_(1)m RNA、MMP-2 m RNA、PBP1A m RNA表达水平。采用偏相关性分析肿瘤组织中TGF-β_(1)m RNA、MMP-2 m RNA、PBP1A m RNA表达水平与复发的关系。采用受试者工作特征(ROC)曲线分析TGF-β_(1)m RNA、MMP-2 mRNA、PBP1A m RNA表达水平对复发的预测价值。结果肿瘤组织中TGF-β_(1)mRNA、MMP-2 m RNA表达水平分别为1.04±0.26、1.45±0.31,明显高于癌旁组织的0.85±0.14、1.18±0.25,PBP1A m RNA表达水平为0.31±0.10,明显低于癌旁组织的0.43±0.12,差异均有统计学意义(P<0.05);列联相关系数C分析显示,肿瘤组织中TGF-β_(1)mRNA、MMP-2 m RNA表达水平与临床分期、浸润深度、淋巴结转移呈正相关(P<0.05),与分化程度呈负相关(P<0.05),而PBP1A m RNA表达水平与临床分期、浸润深度、淋巴结转移呈负相关(P<0.05),与分化程度呈正相关(P<0.05);复发组患者的TGF-β_(1)mRNA、MMP-2 m RNA表达水平分别为1.31±0.25、1.74±0.31,明显高于未复发组的1.01±0.20、1.42±0.25,PBP1A mRNA表达水平为0.18±0.05,明显低于未复发组的0.32±0.10,差异均有统计学意义(P<0.05);偏相关性分析显示,肿瘤组织中TGF-β_(1)mRNA、MMP-2m RNA、PBP1A m RNA表达水平与复发显著相关(P<0.05);TGF-β_(1)mRNA、MMP-2 mRNA、PBP1A mRNA单项及联合预测复发的曲线下面积(AUC)分别为0.755、0.742、0.795、0.915,敏感度为75.00%、70.00%、75.00%、80.00%,特异度为72.25%、67.54%、76.95%、95.81%,且预测效能显著高于各指标单独预测价值(Z=2.376、2.413、1.997,P=0.018、0.016、0.046)。结论Hp阳性早期胃癌患者肿瘤组织中TGF-β_(1)m RNA、MMP-2 m RNA表达水平升高,PBP1A m RNA表达水平降低,且与临床病理特征、复发密切相关,联合检测其水平对复发具有较高的预测价值。
文摘Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) superfamily of proteins, circulates in a complex with vitronectin. Furthermore, these two proteins are co-localized in the extracellular matrix (ECM) in many different pathophysiological conditions. Though PAI-1 is a well-characterized inhibitor of serine proteases, recent emphasis has also focused on its protease-independent functions. Vitronectin, a multi-domain protein that binds a wide variety of ligands and proteins, exists in the circulation in a preferred monomeric state, while in the extracellular matrix it exists as a multimer resulting from an altered conformation. Though the mechanism for the conformational alterations and compartmentalization in tissues is unknown, there are a number of biomolecules including PAI-1 that appear to cause such changes. Experimental analysis has established that PAI-1 induces association of vitronectin to higher-order species in a concentration-dependent fashion [1]. This report extends our investigations into the mechanism of the interaction between vitronectin and PAI-1 to explore the physiological relevance of these higher-order complexes for cellular adhesion and migration. In this study, we evaluate the effects of the pericellular microenvironment on the functions of the multimeric complexes in a variety of relevant biological settings. Our findings underscore the importance of the variability of components within this microenvironment, including different receptors and ECM components, in governing the way in which the vitronectin/PAI-1 complex mediates cell-matrix interactions.
