胃癌组织内MACC1表达与临床病理特征的关系研究

目的 研究胃癌组织内结肠癌转移相关基因-1(MACC1)表达与胃癌患者临床病理特征的关系.方法 选取滨海县人民医院2017年9月至2019年9月收治的88例胃癌患者,入院后通过胃肠镜取其胃癌组织及癌旁正常组织标本,采用免疫组化法测MACC1、肝细胞生长因子(HGF)及肝细胞生长因子受体(c-Met)表达情况,采用RT-...     

MACC1、c-Met蛋白在宫颈癌组织中的表达及其与盆腔淋巴结转移的相关性

目的 研究结肠癌转移相关基因(MACC1)和人原癌基因编码蛋白(c-Met)在宫颈癌组织中的表达及其与盆腔淋巴结转移的相关性.方法 应用免疫组织化学法对MACC1和c-Met蛋白在不同宫颈组织中的表达情况进行检测,分析其表达情况与盆腔淋巴结转移之间的关系.结果 MACC1和c-Met蛋白在宫颈癌组、CINⅡ~Ⅲ组和正常宫颈组中的阳性表达率比较有明显差异(P<0.05);3组间MACC1和c-Met蛋白阳性表达率进行两两比较,差异均有统计学意义(P<0.05).Spearman等级相关性检验结果表明,MACC1和c-Met蛋白的表达呈正相关关系(γ=0.632,P=0.000).肌层浸润深度及MACC1和c-Met蛋白阳性表达是影响宫颈癌盆腔淋巴结转移的独立危险因素(P<0.05).结论 MACC1和c-Met蛋白可能参与了宫颈癌的发生、发展,并与宫颈癌的侵袭转移有关,是宫颈癌盆腔淋巴结转移的独立高危因素,有重要的临床价值.     

MACC1和c-Met蛋白在胃印戒细胞癌中的表达及意义

摘 要：［目的］探讨结肠癌转移相关基因1（metastasis-associated in colon cancer 1,MACC1）和肝细胞生长因子受体（hepatocyte growth factor receptor,c-Met）在胃印戒细胞癌（signet ring cell carcinoma,SRCC）组织中的表达及其与临床病理特征的相关性。［方法］应用免疫组化法检测80例SRCC组织及其对应癌旁组织和25例癌前病变组织中MACC1和c-Met蛋白的表达情况,统计学分析MACC1和c-Met表达水平与临床病理特征的关系。［结果］MACC1和c-Met在SRCC组织中的阳性率均明显高于癌旁组织和癌前病变组织（P＜0.05）。MACC1和c-Met阳性率均与肿瘤浸润深度、TNM分期、淋巴结转移和腹膜转移相关（P<0.05）,而与年龄、性别、肿物部位、大小、CEA和CA199无统计学意义相关（P＞0.05）。SRCC组织中MACC1和c-Met的表达呈正相关（r=0.301,P=0.007)。［结论］MACC1和c-Met在SRCC的侵袭和转移过程中发挥重要作用,有望成为SRCC预后的标志及潜在治疗靶点。     

结肠癌转移相关基因1与肿瘤转移

新近研究发现,结肠癌转移相关基因1( MACC1)在人类多种肿瘤中存在异常高表达,作为肝细胞生长因子-酪氮酸激酶受体(HGF-MET)信号通路的关键调控者,可以明显上调MET蛋白的表达,促进肿瘤细胞的运动、侵袭和转移.进一步的研究将有助于阐明肿瘤转移的机制,同时也为肿瘤转移靶向治疗提供了新思路.     

肺腺癌组织中MACC1和c-Met蛋白的表达及其与患者术后复发的关系

目的 检测MACC1、c-Met蛋白在肺腺癌组织中的表达,及其在患者术后复发中的预测价值。方法 收集完全性切除的肺腺癌患者术后病理标本102例和癌旁组织57例,采用免疫组织化学技术检测MACC1和c-Met蛋白在肺腺癌和癌旁组织中的表达,对患者行定期随访,分析MACC1和c-Met 蛋白的表达与患者术后复发的关系。结果 MACC1和c-Met在癌组织中的阳性表达率分别为59.80%、54.90%,明显高于癌旁组织中的7.01%、10.53%,差异有统计学意义（P<0.05）。MACC1、c-Met蛋白的表达与性别年龄无关,与肿瘤T分期、淋巴结转移、病理TNM分期有关（P<0.05）。MACC1与c-Met 的表达之间呈正相关（r=0.262, P=0.008）。MACC1阳性组2年内复发率为73.77%,明显高于阴性组的31.71%（χ²=17.686, P<0.001）。c-Met阳性组2年内复发率为76.79%,高于阴性组的34.78%（χ²=18.272, P<0.001）。Cox回归多因素提示MACC1和c-Met蛋白的表达、术后病理分期、肿瘤T分期及淋巴结转移情况是腺癌患者复发转移的危险因素。结论 MACC1和c-Met蛋白在肺腺癌组织中表达与肿瘤T分期、淋巴结转移、病理分期有关,影响肺腺癌患者术后无瘤生存期,是复发转移的危险因素。     

MACC1和c-met在非小细胞肺癌中的表达及其预后价值

背景与目的已有的研究表明结肠癌转移相关基因1(metastasis-associated in colon cancer1,MACC1)是一个与肿瘤浸润转移相关的新基因,该基因能够调节肝细胞生长因子受体(hepatocyte growth factor receptor,c-met)的表达。本研究旨在探讨MACC1和c-met在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其与浸润转移和预后的关系。方法采用免疫组化检测103例NSCLC组织及40例癌旁正常组织中MACC1和c-met蛋白的表达。结果 MACC1和c-met在NSCLC组中的阳性表达率均明显高于正常肺组织(P<0.001)。MACC1和c-met阳性率均与肺癌的分化程度、T分期、淋巴结转移和TNM分期相关(P<0.05),而与性别、年龄、吸烟及组织学类型等无关(P>0.05)。MACC1和c-met的表达呈正相关(r=0.403,P<0.001)。Kaplan-Meier生存曲线显示MACC1和c-met阳性组5年生存率均明显低于阴性组(P<0.05)。Cox多因素分析显示MACC1是NSCLC的独立预后因素(P=0.026)。结论 MACC1和c-met的表达与肺癌的分化、浸润和转移密切相关,两者均对生存期有一定的影响,MACC1是NSCLC的独立预后危险因素。     

MACC1与妇科肿瘤的研究进展

摘 要：MACC1是新近发现的与结肠癌的发生和转移密切相关的基因。体外研究发现MACC1能够诱导肿瘤细胞的增生、增殖及迁移,是HGF/c-Met信号通路中Mrt基因的关键调节因子,在妇科肿瘤的发生及发展中也起主要的作用。近年发现MACC1异常表达与宫颈癌、卵巢癌和子宫内膜癌的转移和预后密切相关,可作为判断这些恶性肿瘤转移和预后的肿瘤标志物。全文就MACC1与妇科恶性肿瘤的关系作一阐述。     

结肠癌转移相关基因1对结肠癌细胞肝转移的影响

目的:研究结肠癌转移相关基因1(metastasis-associated in colon cancer1,MACC1)的表达对结肠癌肝转移的影响。方法:将融合绿色荧光蛋白(green fluorescent proteins,GFP)的慢病毒表达载体分别感染具有不同转移潜能的人结肠癌细胞株SW1116和HCT116。给予BALB/c-nu/nu裸鼠脾脏注射感染后的结肠癌细胞,构建结肠癌肝转移模型。注射后35d,在荧光解剖显微镜下观察肝脏内结肠癌细胞的转移情况,计算肝转移率。应用蛋白质印迹法检测SW1116和HCT116细胞中MACC1蛋白的表达水平,评估MACC1的表达水平与肝转移率的关系。结果:SW1116细胞的肝转移率明显高于HCT116细胞。MACC1蛋白在HCT116细胞中呈低表达,而在SW1116细胞中呈高表达,差异有统计学意义(P<0.01)。结论:MACC1蛋白的表达水平可能与结肠癌的肝转移能力呈正相关。     

MACC1和C-met蛋白在食管癌中的表达及意义

目的:观察结肠癌转移相关基因（MACC1）和肝细胞生长因子受体（C-met）蛋白在食管癌中的表达及意义。方法:采用免疫组织化学EnVinsion法检测88例食管癌组织中MACC1和C-met蛋白的表达情况,分析两者与食管癌病理分级、临床分期的关系及两者在食管癌组织中表达的相关性。结果:MACC1和C-met在食管癌组织中的阳性率分别为88.64％和75.00％。在食管癌中MACC1和C-met蛋白高表达与临床分级、分期显著相关（P<0.001）。进一步分析显示食管癌组织中MACC1和C-met蛋白表达具有相关性。结论:食管癌组织中MACC1、C-met及其蛋白表达水平增高,C-met通路的激活和MACC1过表达可能与食管癌的发生、发展有关,MACC1和C-met具有作为食管癌分子标志物的潜在价值。     

MACC1基因在结肠癌中的表达及其临床意义

目的探讨MACC1基因在结肠癌组织中的表达及临床意义。方法收集80例结肠癌手术标本及20例正常的肠黏膜标本,用免疫组化法检测MACC1基因在标本中的表达情况。结果 MACC1基因在正常肠黏膜中不表达,在结肠癌中高表达。MACC1基因的表达水平与TNM分期和肿瘤浸润深度、淋巴结转移、组织学分化程度、Ki-67和p53基因的表达水平相关。结论 MACC1基因在正常结肠黏膜组织中不表达,在结肠癌组织中有较高的阳性表达率。MACC1基因的表达可作为预测结肠癌转移和预后的生物学指标。     

A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients

Background  

The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Deregulation of HGF/MET signaling is reported as a prognostic marker for tumorigenesis, early stage invasion, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients.     

Metastasis‐associated in colon cancer‐1 upregulation predicts a poor prognosis of gastric cancer,and promotes tumor cell proliferation and invasion

Metastasis‐associated in colon cancer‐1 (MACC1) is a newly identified oncogene, and little is known about its role in gastric cancer (GC). Our study was performed to investigate whether MACC1 influences the prognosis of GC patients and to explore the potential mechanisms involved. MACC1 expression was verified to be higher in GC tissues than in adjacent nontumorous tissues by Western blotting. A retrospective analysis of 361 GC patients (Stages I–IV) revealed that higher MACC1 expression was associated with more advanced disease, more frequent postoperative recurrence, more metastases and a higher mortality rate. The disease‐free survival of Stage I–III patients and overall survival of Stage‐IV patients were significantly worse when their tumors showed high MACC1 expression. To investigate the underlying mechanisms, MACC1 overexpression and downregulation were established in two GC cell lines (BGC‐823 and MKN‐28 cells). MACC1 overexpression significantly accelerated tumor growth and facilitated metastasis in athymic mice. MACC1 also promoted the proliferation, migration and invasion of both GC cell lines. Moreover, gastric MACC1 mRNA expression levels were significantly correlated with markers of the epithelial‐to‐mesenchymal transition (EMT) in patients with GC. MACC1 overexpression upregulated mesenchymal–epithelial transition factor and induced changes to markers of EMT, whereas silencing of MACC1 reversed all these changes. These findings provide some novel insights into the role of MACC1, a gene that contributes to a poor prognosis of GC by promoting tumor cell proliferation and invasion as well as the EMT.     

Overexpression of Metastasis-Associated in Colon Cancer-1 Associated with Poor Prognosis in Patients with Esophageal Cancer

Recent studies have shown that expression of metastasis-associated in colon cancer-1(MACC1) is observed in different types of cancer and plays an important role in tumor metastasis. However, the expression of MACC1 and its possible role in esophageal cancer remains unknown. In this study, we determined the expression of MACC1 in esophageal cancer by utilizing immunohistochemistry and analyzed the relationship between the expression and esophageal cancer prognosis. Immunohistochemistry results showed that 47 of 85 cancer lesions (55.2 %) were stained positive, and high expression of MACC1 was correlated with the node metastasis and TNM stage (P?<?0.05). The Kaplan-Meier survival curve showed that patients with high MACC1 expression had significantly reduced overall 5-year survival rates (P?=?0.004). Cox regression analysis revealed that high expression of MACC1 was associated with increased risk of death (hazard ratio [HR] =2.25) in patients with esophageal cancer. These findings suggested that high expression of MACC1 was correlated with progression and metastasis of esophageal cancer and might serve as a novel prognostic marker for patients with esophageal cancer.     

Metastasis-associated in colon cancer-1 promotes vasculogenic mimicry in gastric cancer by upregulating TWIST1/2

Vasculogenic mimicry (VM) is a blood supply modality that is strongly associated with the epithelial-mesenchymal transition (EMT), TWIST1 activation and tumor progression. We previously reported that metastasis-associated in colon cancer-1 (MACC1) induced the EMT and was associated with a poor prognosis of patients with gastric cancer (GC), but it remains unknown whether MACC1 promotes VM and regulates the TWIST signaling pathway in GC. In this study, we investigated MACC1 expression and VM by immunohistochemistry in 88 patients with stage IV GC, and also investigated the role of TWIST1 and TWIST2 in MACC1-induced VM by using nude mice with GC xenografts and GC cell lines. We found that the VM density was significantly increased in the tumors of patients who died of GC and was positively correlated with MACC1 immunoreactivity (p < 0.05). The 3-year survival rate was only 8.6% in patients whose tumors showed double positive staining for MACC1 and VM, whereas it was 41.7% in patients whose tumors were negative for both MACC1 and VM. Moreover, nuclear expression of MACC1, TWIST1, and TWIST2 was upregulated in GC tissues compared with matched adjacent non-tumorous tissues (p < 0.05). Overexpression of MACC1 increased TWIST1/2 expression and induced typical VM in the GC xenografts of nude mice and in GC cell lines. MACC1 enhanced TWIST1/2 promoter activity and facilitated VM, while silencing of TWIST1 or TWIST2 inhibited VM. Hepatocyte growth factor (HGF) increased the nuclear translocation of MACC1, TWIST1, and TWIST2, while a c-Met inhibitor reduced these effects. These findings indicate that MACC1 promotes VM in GC by regulating the HGF/c-Met-TWIST1/2 signaling pathway, which means that MACC1 and this pathway are potential new therapeutic targets for GC.