MMP-2、MMP-9及P53的表达在肝移植后肿瘤复发与转移预测中的价值研究

目的：探讨MMP-2、MMP-9及P53的表达在预测肝癌行肝移植后肿瘤复发与转移中的价值。方法：选择肝癌行全肝移植患者85例,应用免疫组化方法检测其切除的肝癌组织中MMP-2、MMP-9及P53的表达,并对患者进行移植术后随访,观察术后肝癌复发与转移情况。分析MMP-2、MMP-9及P53的表达与移植后肝癌复发与转移之间的关系和意义。结果：肝癌组织中MMP-2、MMP-9及P53阳性表达率均明显高于癌旁组织（P〈0.01）。MMP-2表达与肝癌肿瘤直径、TNM分期、病理分级及门静脉癌栓显著相关性（P〈0.05）,MMP-9表达与肝癌肿瘤直径、TNM分期、门静脉癌栓及肿瘤包膜显著相关性（P〈0.05）,P53表达与肝癌肿瘤直径、门静脉癌栓及肿瘤包膜显著相关性（P〈0.05）。MMP-2、MMP-9在未复发和转移组中的表达明显低于复发和转移组（P〈0.05）,而P53在两组间的表达差异无显著性（P〉0.05）。肝癌组织中MMP-2、MMP-9高阳性表达均是预测肝癌患者肝移植后肿瘤复发和转移的独立预见因子,而P53未显示其具有预测意义。结论：MMP-2、MMP-9及P53在肝癌组织中呈高表达,MMP-2、MMP-9的表达水平可以有效预测肝癌患者肝移植后肿瘤复发和转移。     

MMP-2、MMP-7、MMP-9、TIMP-1及TIMP-2在乳腺癌组织中的表达及意义

目的:探讨基质金属蛋白酶及其抑制剂在乳腺癌组织中的表达及其与肿瘤浸润转移的关系,为乳腺癌的临床治疗及预后预测提供基础。方法:选择我院2012年5月至2014年5月收治的乳腺癌患者80例,对所选病例的乳腺癌组织、癌旁组织及正常乳腺组织样本进行检测。观察并比较不同乳腺组织中MMP-2,MMP-7、MMP-9、TIMP-1及TIMP-2 m RNA的表达水平。结果:与正常乳腺组织相比较,乳腺癌组织和癌旁组织中MMP-2、MMP-7、MMP-9,TIMP-1及TIMP-2 m RNA的表达显著增加,差异具有统计学意义(P0.05)。乳腺癌组织中MMP-2、MMP-7、MMP-9、TIMP-1及TIMP-2 m RNA的表达显著高于癌旁组织和正常组织,差异具有统计学意义(P0.05)。随着肿瘤范围扩大,MMP-2、MMP-7和MMP-9 m RNA的表达水平显著增加(P0.05),而TIMP-1和TIMP-2 m RNA表达无显著变化(P0.05)。随着淋巴结转移进展,MMP-2、MMP-7和MMP-9 m RNA的表达显著增加(P0.05),而TIMP-1和TIMP-2 m RNA无显著变化(P0.05)。结论:MMP-2、MMP-7、MMP-9、TIMP-1和TIMP-2的m RNA在乳腺癌组织中呈高表达,这可能与乳腺癌的发生和发展有关,而MMP-2、MMP-7和MMP-9可能有助于预测乳腺癌的侵袭行为。     

三阴性乳腺癌中MMP9和P53的表达与其预后的关系研究

目的:研究三阴性乳腺癌(triple negative breast cancer,TNBC)中基质金属蛋白酶9(matrix metal proteinase 9,MMP9)和P53的表达及其与三阴性乳腺癌预后的关系。方法:收集2002年3月至2011年7月上海交通大学医学院附属新华医院普外科诊治且临床资料完整的TNBC标本147例,通过免疫组化检测其MMP9、P53的表达。结合临床随访数据,分析MMP9、P53的表达与TNBC预后的关系。结果:TNBC占同期本院收治的乳腺癌13.3%(147/1103)。MMP9、P53在TNBC中的阳性表达率分别为47.6%和66.0%。MMP9与TNBC患者的淋巴结转移数显著相关(P=0.003)。MMP9表达阳性的TNBC与MMP9表达阴性TNBC患者60个月的无病生存(disease free survival,DFS)率分别为62%和83%,差异具有统计学意义(P=0.001);总体生存率(overall survival,OS)率分别为66%和73%,差异具有统计学意义(P=0.022)。P53表达阳性的TNBC和P53表达阴性的TNBC患者60个月的DFS分别为65%和87%(P=0.010);OS分别为60%和85%(P=0.005)。MMP9和P53的HR分别为3.353(95%CI:1.614-6.966,P=0.001)和2.979(95%CI:1.239-7.165,P=0.015)。结论:MMP9和P53在TNBC中的阳性表达与患者的预后不良有关,且MMP9为影响TNBC患者预后的独立危险因素。     

血清P53、MMP-7抗体表达与食管癌的病理类型、分期的相关性

目的:探讨血清P53、基质金属蛋白酶-7(Matrix metalloproteinase-7,MMP-7)抗体表达与食管癌的病理类型、分期的相关性.方法:2019年10月-2020年4月选择在本院诊治的食管癌患者80例作为食管癌组,同期选择体检的健康人50例作为对照组,检测两组血清P53、MMP-7抗体表达情况,调查...     

HIF-lα的表达在肝移植后肝癌复发与转移中的意义

目的：探讨肝癌组织中低氧诱导因子-lα（HIF-lα）表达与肝癌行肝移植治疗后肿瘤复发与转移之间的关系。方法：选择肝癌行全肝移植患者45例,应用免疫组化方法检测其切除的肝癌组织、癌旁组织中HIF-lα的表达,分析其表达与移植后肝癌复发与转移之间的关系和意义。结果：肝癌组织中HIF-1α阳性表达率明显高于癌旁组织（X2=6.39,P〈0.01）。HIF-1α在肝癌组织中的表达与肿瘤直径、TNM分期、有无淋巴结转移、有无门静脉癌栓及肿瘤播散灶密切相关（P〈0.01）。复发转移组和未复发转移组HIF-1α阳性表达率比较,差异存在显著性（X2=8.46,P〈0.01）。Cox回归多因素分析表明HIF-1α高表达是影响肝癌患者肝移植后肿瘤复发和转移的独立预后因素（P〈0.01）。结论：HIF-1α蛋白有望成为一个预测肝癌患者肝移植后复发和转移的重要指标。     

C-erBb-2、MMP-9 在结直肠癌中的表达及相关意义

目的:探讨C-erBb-2、基质金属蛋白酶-9(MMP-9)在结直肠癌中的表达与其浸润转移的关系,寻找浸润转移的客观指标及可能相关机制。方法:用免疫组化法测定80例结直肠癌组织中C-erBb-2和MMP-9的表达情况。结果:①C-erBb-2、MMP-9在结直肠癌组织中阳性表达率60.0%,(48/80)和56.2%(45/80)。②在有淋巴结转移的结直肠癌组织中C-erBb-2、MMP-9阳性率分别为75.0%(30/40)、72.5%(29/40),高于无淋巴结转移的结直肠癌组织中的C-erBb-2、MMP-9阳性率45%(18/30)、40.0%(16/40),(P<0.05);③二者共同阳性者淋巴结转移率为78.1%(25/32)高于二者均阴性者淋巴结转移率26.3%(5/19),(P<0.05),④C-erBb-2、MMP-9联合表达存在意义,且为正相关(r=0.257,P<0.05)。⑤C-erBb-2、MMP-9的表达与肿瘤的大小、性别、年龄、浸润层次等因素无关,但与肿瘤分期、淋巴结转移、分化有关。结论:C-erBb-2、MMP-9表达与淋巴结转移密切相关,二者在有淋巴结转移的结直肠癌组织中表达可能存在协同作用,可作为临床检测淋巴结转移的重要指标之一。     

HIF-1α的表达在肝移植后肝癌复发与转移中的意义

目的:探讨肝癌组织中低氧诱导因子-1α(HIF-1α)表达与肝癌行肝移植治疗后肿瘤复发与转移之间的关系.方法:选择肝癌行全肝移植患者45例,应用免疫组化方法检测其切除的肝癌组织、癌旁组织中HIF-1α的表达,分析其表达与移植后肝癌复发与转移之间的关系和意义.结果:肝癌组织中HIF-1α阳性表达率明显高于癌旁组织(X<'2>=6.39,P<0.01).HIF-1α在肝癌组织中的表达与肿瘤直径、TNM分期、有无淋巴结转移、有无门静脉癌栓及肿瘤播散灶密切相关(P<0.01).复发转移组和未复发转移组HIF-1α阳性表达率比较,差异存在显著性(X<'2>=8.46,P<0.01).Cox回归多因素分析表明HIF-1α高表达是影响肝癌患者肝移植后肿瘤复发和转移的独立预后因素(P<0.01).结论:HIF-1α蛋白有望成为一个预测肝癌患者肝移植后复发和转移的重要指标.     

MMP-2、MMP-9及VEGF在子宫内膜异位症中的表达及临床意义

目的:研究基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、血管内皮生长因子(VEGF)表达在子宫内膜异位症发生发展中的作用.方法:应用免疫组化二步法检测EMs患者异位内膜36例、在位内膜36例及正常内膜中的MMP-2、MMP-9、VEGF的表达情况.结果:MMP-2、MMP-9、VEGF在异位内膜组中阳性表达率分别为94.4%、91.7%和91.7%,显著高于在位内膜组、正常内膜组(P＜0.05);而在位内膜组和正常内膜组差异无统计学意义(P＞0.05).结论:检测MMP-2、MMP-9、VEGF的表达可用于判断子宫内膜异位症的侵袭转移和评估预后.     

瘢痕疙瘩及增生性瘢痕中MMP-2、MMP-9的表达

目的探讨基质金属蛋白酶-2、基质金属蛋白酶-9(MMP-2、MMP-9)在瘢痕疙瘩(keloid,Ke)及增生性瘢痕中(hypertrophic scar,HS)的表达。方法免疫组织化学SP法检测MMP-2、MMP-9在20例瘢痕疙瘩、15例增生性瘢痕及10例正常皮肤中的表达,采用图像分析技术对免疫组化结果进行定量分析。结果Ke中MMP-2表达高于正常皮肤(t=2.366,P<0.05),高于HS(t=2.223,P<0.05);MMP-9表达高于正常皮肤(t=3.198,P<0.01),高于HS(t=2.110,P<0.05)。HS中MMP-2表达与正常皮肤无差异(t=0.218,P>0.05),MMP-9表达与正常皮肤无差异(t=1.873,P>0.05)。正常人皮肤仅见MMP-2、MMP-9蛋白的弱阳性或阴性表达。结论MMP-2、MMP-9蛋白的表达与皮肤损伤后的过度增殖及肿瘤化倾向有关。     

MMP-2及TIMP-2的表达与胶质瘤复发相关性的研究

目的:探讨基质金属蛋白酶类与胶质细胞瘤浸润性生长之间的关系及其在胶质瘤复发中的作用。以及基质金属蛋白酶及其抑制因子(MMP-2、TIMP-2)的阳性表达与胶质细胞瘤病理分级及预后的关系。方法:应用免疫组织化学染色法(SP法)检测48例人脑原发和复发胶质细胞瘤组织中MMP-2、TIMP-2的表达。结果:Ⅲ、Ⅳ级和复发胶质细胞瘤中的MMP-2蛋白的表达显著高于Ⅰ、Ⅱ级(P<0.05);Ⅰ、Ⅱ级胶质细胞瘤中的TIMP-2蛋白的表达显著高于复发胶质细胞瘤(P<0.05)而与Ⅲ、Ⅳ级细胞瘤无显著性差异(P>0.05);Ⅲ、Ⅳ级和复发胶质细胞瘤中的MMP-2,TIMP-2蛋白的表达无显著差异(P>0.05);同级别胶质细胞瘤中MMP-2、TIMP-2的表达之间无明显相关性(P>0.05);正常脑组织中无表达。结论:MMP-2、TIMP-2的表达与胶质细胞瘤的恶性程度有关,低级别中,MMP-2与TIMP-2成正相关;MMP-2的高表达,TIMP-2的低表达与胶质细胞瘤的侵袭有关,MMP-2、TIMP-2的表达水平有可能成为判定胶质细胞瘤恶性程度、侵袭能力和预后的诊断指标,而且TIMP-2可能更加敏感。     

p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53

p53 mutations, occurring in two-thirds of all human cancers, confer a gain of function phenotype, including the ability to form metastasis, the determining feature in the prognosis of most human cancer. This effect seems mediated at least partially by its ability to physically interact with p63, thus affecting a cell invasion pathway, and accordingly, p63 is deregulated in human cancers. In addition, p63, as an 'epithelial organizer', directly impinges on epidermal mesenchimal transition, stemness, senescence, cell death and cell cycle arrest, all determinant in cancer, and thus p63 affects chemosensitivity and chemoresistance. This demonstrates an important role for p63 in cancer development and its progression, and the aim of this review is to set this new evidence that links p63 to metastasis within the context of the long conserved other functions of p63.     

A pilot study of recurrence of human glial tumours in light of p53 heterozygosity status

Genetic alterations in the p53 tumour suppressor gene of human chromosome 17 have been frequently found to be associated with various tumours. Glial tumours arise from the supporting cells of the brain. They have a poor outcome and often recur. The present study was undertaken to compare the loss of heterozygosity (LOH) of p53 gene in pairs of primary and recurrent gliomas and to try and correlate it to the degree of malignancy and recurrence interval. LOH of p53 was taken as an indicator of the inactivation of p53 due to genetic changes. Ten patients with recurrent gliomas were studied. Three patients had LOH at primary surgery and two of these had LOH at recurrent surgery. One patient had LOH of p53 only at recurrent surgery but not at primary surgery. No indicative correlation was found between p53 heterozygosity status on one hand and grade of malignancy (primary and recurrent) and recurrence interval on the other.     

p53R2 overexpression in cervical cancer promotes AKT signaling and EMT,and is correlated with tumor progression,metastasis and poor prognosis

p53R2 is a p53-inducible ribonucleotide reductase subunit involved in deoxyribonucleotide biosynthesis and DNA repair. Although p53R2 has been linked to human cancer, its role in cervical cancer remains unknown. In this study, we investigated the expression and clinical significance of p53R2 in early-stage cervical cancer. p53R2 expression is significantly upregulated at both mRNA and protein levels in cervical cancer cells and tissues, compared with that in matched normal cervical cells and tissues, respectively. p53R2 overexpression is associated with increased risk of pelvic lymph node metastasis (PLNM, p = 0.001) and cancer relapse (p = 0.009). Patients with high p53R2 expression have a shorter overall survival (OS) and disease-free survival (DFS). p53R2 is an independent factor for predicting OS and DFS of cervical cancer patients. We further show that p53R2 is important for oncogenic growth, migration and invasion in cervical cancer cells. Mechanistically, p53R2 promotes Akt signaling and epithelial–mesenchymal transition (EMT). In conclusion, our study demonstrates for the first time that p53R2 protein is overexpressed in early-stage cervical cancer and unravels some unconventional oncogenic functions of p53R2. p53R2 may be a useful prognostic biomarker and therapeutic target for cervical cancer.     

WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression

WAVE3 is a member of the WASP/WAVE family of proteins, which play a critical role in the regulation of actin polymerization, cytoskeleton organization, and cell motility. We show here that knockdown of the WAVE3 protein, using RNA interference in MDA-MB-231 cells, decreases phospho-p38 MAPK levels, but not those of phospho-AKT, phospho-ERK, or phospho-JNK. Knockdown of WAVE3 expression also inhibited the expression levels of MMP-1, MMP-3, and MMP-9, but not MMP-2. MMP production could be restored by PMA treatment, without affecting siRNA-mediated WAVE3 knockdown. The WAVE3-mediated downregulation of p38 activity and MMP production is independent of the presence of both WAVE1 and WAVE2, whose expression levels were not affected by loss of WAVE3. We also show that the downstream effect of the WAVE3 knockdown is the inhibition of cell motility and invasion, coupled with increased actin stress fiber formation, as well as reorganization of focal adhesion complexes. These findings suggest that WAVE3 regulates actin cytoskeleton, cell motility, and invasion through the p38 MAPK pathway and MMP production.     

Gene expression profiling of p53-sensitive and -resistant tumor cells using DNA microarray

Overexpression of wild-type p53 in ECV-304 tumor cells induced extensive apoptosis and the eventual death of nearly all of the cells. We generated ECV-304 cells resistant to p53-induced apoptosis as a strategy to identify novel genes that might be relevant to p53-mediated apoptosis. ECV-304 cells resistant to p53 were isolated by repeated infections with a recombinant p53 adenovirus and were designated as DECV. The expression of 5,730 genes in p53-resistant (DECV) and p53-sensitive ECV-304 cells were profiled by DNA microarray analysis. We report here the expression of 80 genes that differed by 2-fold or more between sensitive and resistant cells upregulated for p53. Many of these differentially expressed genes are regulated by p53 in ECV-304 and H1299 p53-null cells. Our analysis identifies many new potential targets for p53 that play roles in cell cycle regulation, DNA repair, redox control, cell adhesion, apoptosis, and differentiation.     

Regulation of VEGF, MMP-9 and metastasis by CXCR4 in a prostate cancer cell line

To investigate the mechanisms involved in PCa (prostate cancer) metastasis and CXCR4 (CXC chemokine receptor-4)-mediated VEGF (vascular endothelial growth factor) and MMP-9 (matrix metalloproteinase-9) expression, we used lentivirus-mediated RNAi (RNA interference) to reduce the expression of CXCR4 in a PCa cell line. We found that the silencing of CXCR4 led to a significant down-regulation of VEGF and MMP-9 at both the mRNA and protein levels compared with the control in vitro. Using an animal model, we confirmed that CXCR4 silencing via subcutaneous injection could reduce tumour growth as well as inhibit metastasis, particularly bone metastasis, of PCa. Using in vivo immunohistochemistry, we also found that the expression of VEGF and MMP-9 were reduced by the knockdown of CXCR4 in the primary tumours of mice. Collectively, our results indicate that CXCR4 plays an important role in PCa metastasis through the up-regulation of VEGF and MMP-9. These findings may aid future intervention strategies.     

P53 Codon 72多态性、P53表达与宫颈癌放疗敏感性相关性的研究

目的：研究P53 Codon 72多态性、P53的表达与宫颈癌放疗敏感性的相关性。方法：Ib2期宫颈癌患者274例,术前192Ir腔内后装4次,A点放疗剂量2400cGy,一周2次,共2周。治疗后14d进行广泛性子宫切除。据术后病理放疗反应HE染色结果分为放疗敏感与放射抗拒两组。免疫组化sP法检测P53蛋白在治疗前宫颈癌组织中的表达,分析放疗敏感与放射抗拒两组P53蛋白表达差异有无显著性意义;采用PCR后测序的方法检测治疗前P53第72密码子的基因型频率多态性（P53 Codon 72）。分析放疗敏感与放射抗拒两组中各P53 Codon 72基因型的差异有无显著性意义。结果：放疗抗拒组与放疗敏感组相比。P53高表达的比例显著高于P53低表达的比例（P=O．00081）。P53 Codon 72多态性分析,Pro／Pro与Arg／Arg、Pro／Pro与Arg／Pro在放疗敏感组与放疗抗拒组的分布差异显著（P值分别为P=0．009和P=0．032）;Arg／Arg与Arg／Pro,在放疗敏感组与放疗抗拒组的分布无显著差异（P=O．503）。结论：P53Codon72多态性和P53蛋白与宫颈癌放疗敏感性有相关性,可以作为早期宫颈癌放疗敏感性的预测指标。