TFF2、CLDN18、MUC5AC蛋白在胃黏膜病变过程中的表达变化及其临床意义

背景:胃癌是我国发病率和死亡率最高的恶性肿瘤之一,胃黏膜病变过程中早期分子标记是近年胃癌研究的重点。目的:探讨三叶因子2(TFF2)、闭合蛋白18(CLDN18)和黏蛋白5AC(MUC5AC)在不同胃黏膜病变中的表达情况及其临床意义。方法:选取2008年12月-2009年5月内蒙古自治区人民医院的胃镜活检和手术标本71例,其中正常胃黏膜组织20例,肠化生组织20例,异型增生组织11例,胃癌组织20例,采用免疫组化SP法检测TFF2、CLDN18和MUC5AC蛋白表达情况。结果:正常胃黏膜组织中TFF2、CLDN18和MUC5AC蛋白均为阳性表达,表达率为100%,而肠化生、异型增生以及胃癌组织中,三种蛋白阳性表达率依次逐渐下降,组间差异有统计学意义(P0.01)。结论:TFF2、CLDN18和MUC5AC蛋白表达水平与胃黏膜组织恶性程度密切相关,是潜在的预测胃癌发生、发展和预后的重要生物学标记。     

胰腺导管内乳头状黏液性肿瘤组织中MUC1,MUC2,MUC5AC和TFF1的表达意义

目的:了解胰腺导管内乳头状黏液性肿瘤(IPMN)中MUC1,MUC2,MUC5AC及TFF1的表达意义.方法:采用免疫组织化学方法,检测IPMN手术切除标本9例中MUC1,MUC2,MUC5AC及TFF1的表达,分析不同组织学类型及不同性质IPMN之间黏液蛋白及TFF1表达的差异.结果:MUC1表达率为44.4%,MUC2为66.7%,MUC5AC和TFF1为100%.胃型IPMN黏液蛋白表达模式主要为MUC1-,MUC2-,MUC5AC .肠型IPMN为MUC1-,MUC2 ,MUC5AC .嗜酸性细胞型IPMN为MUC1 ,MUC2 ,MUC5AC .IPMN相关管状癌MUC1阳性,胶质癌MUC2阳性.MUC5AC和TFF1共同表达,在浸润癌中表达下降.胃型IPMN常与其他类型IPMN同时出现并且不同上皮之间出现移行过渡,提示胃型可能是其他类型IPMN的前期病变.结论:不同组织学亚型的IPMN具有不同的黏液蛋白表达模式.MUC1表达提示侵袭性生物.     

EGFR、PCNA和MUC5AC在阿司匹林相关人胃黏膜病变中的表达

目的 分析阿司匹林相关人胃黏膜病变组织中EGFR、PCNA、MUC5AC的表达，阐明其在阿司匹林相关胃黏膜病变中的作用。方法 严格按照纳入标准，收集2020年8月至2021年12月于清华大学第一附属医院消化内科确诊的阿司匹林相关胃黏膜病变组织(42例)作为阿司匹林组，同期健康体检者相对正常胃黏膜组织(25名)作为健康对照组，采用免疫组织化学SP法检测胃黏膜组织中EGFR、PCNA、MUC5AC的表达情况。结果 根据染色强度、细胞阳性率与染色强度乘积的半定量法及ImageJ软件半定量法三种方法分析均发现，与健康对照组相比，阿司匹林相关人胃黏膜病变组织中EGFR、PCNA、MUC5AC表达均明显升高(P<0.05)。结论 阿司匹林相关人胃黏膜病变组织中EGFR、PCNA、MUC5AC蛋白表达均上调，共同参与了阿司匹林相关胃黏膜病变的发生、发展过程。     

“湿”证与幽门螺旋杆菌感染的相关性及对胃黏液蛋白MUCA5AC、MUC6、MUC1表达的影响

[目的]探索"湿"证与幽门螺旋杆菌(HP)感染的相关性及对胃黏膜屏障中胃黏液蛋白MUCA5AC、MUC6、MUC1表达的影响。[方法]以随机数字表法将研究对象分为观察组(湿证)和对照组(健康体检人群),每组各80例,研究与HP感染的相关性,并进一步探索2组胃黏膜中MUCA5AC、MUC6、MUC1因子的表达情况。[结果]湿证组中HP阳性率明显高于对照组,2组之间差异有统计学意义(P<0.05)。湿证与HP感染呈正相关(r=0.681,P<0.01)。观察组胃黏膜中MUCA5AC、MUC6、MUC1因子表达明显低于对照组(P<0.05)。[结论]湿邪能降低胃黏膜屏障中黏液蛋白的表达,破坏胃黏膜屏障,可能是HP感染或复发的关键病理因素。     

血清MUC1、MUC2及MUC5AC表达与胃癌的关系

目的:探讨胃癌血清中MUC1、MUC2及MUC5AC与胃癌的关系.方法:利用黏蛋白MUC1、MUC2及MUC5AC的单抗及多抗,制备黏蛋白芯片,用免疫荧光原理进行检测,并用CEA作为指示指标,对30例胃癌患者及30例健康人进行黏蛋白血清水平的检测.结果:胃癌组与对照组相比,3种黏蛋白血清水平均增高,两组间差异显著.MUC1的阳性表达与胃癌TNM分期相关(P=0.0047),MUC2和MUC5AC的阳性表达与TNM分期无关(P=0.136.P=0.201).3种黏蛋白的表达均随胃癌分化程度降低而阳性表达增高的趋势,各单一黏蛋白以及黏蛋白两两之间联合用于胃癌诊断的敏感性及特异性均较高,其中单一黏蛋白中,MUC1的的敏感性和特异性最好,分别达到81.5%、75.8%,联合诊断(3种黏蛋白中至少2种阳性)的敏感性和特异性达到96.0%、82.9%.结论:检测血清黏蛋白MUC1、MUC2及MUC5AC水平,可以提高胃癌诊断的敏感性及特异性,为早期诊断提供新的思路,并对判断分期及预后提供帮助.     

中西医结合治疗对消化性溃疡胃黏膜黏蛋白5AC和内皮素-A受体mRNA的影响

[目的]探讨中西医结合治疗对消化性溃疡(PU)患者胃黏膜黏蛋白5AC(MUC5AC)和内皮素-A受体(ETAR)mRNA表达的影响.[方法]在纤维胃镜下取PU患者治疗前溃疡边缘及正常胃黏膜和治疗后溃疡瘢痕边缘胃黏膜,提取mRNA,应用逆转录多聚酶链式反应技术对MUC5AC mRNA和ETAR mRNA的表达进行半定量测定.[结果]中西医结合、中药治疗均可以上调PU患者MUC5AC mRNA的表达,以中西医结合治疗上调的更明显(P＜0.01);中西医结合、中药、西药治疗均可下调ETARmRNA的表达,以中西医结合治疗下调的更明显(P＜0.01);内镜下溃疡病分期与MUC5AC和ETAR mRNA的表达分别呈正和负相关(r值为0.910 0和-0.885 0,P＜0.01),MUC5AC和ETAR mRNA表达呈中等程度负相关(r=-0.537 0,P＜0.01).[结论]中西医结合治疗通过改善胃黏膜MUC屏障保护作用和血流量促进溃疡愈合,且较单用中药或西药疗效更好.     

二陈汤对慢性支气管炎气道黏液高分泌的影响

目的观察二陈汤对慢性支气管炎大鼠气道黏液高分泌的影响及其机制。方法采用香烟烟熏加内毒素脂多糖制备慢性支气管炎大鼠模型,大鼠随机分为正常组,模型组,二陈汤低、中、高剂量组,急支糖浆组。正常组和模型组灌胃生理盐水6 ml/d,急支糖浆组灌胃给予太极急支糖浆12 g/kg,二陈汤低、中、高剂量组分别灌胃2.45、4.90、9.80 g/kg,连续14 d。免疫组化检测黏蛋白(MUC)5AC和水通道蛋白(AQP)5在支气管组织中的表达。结果与正常组相比,模型组MUC5AC蛋白表达显著增强,AQP5蛋白表达显著减弱(均P0.01),MUC5AC与AQP5蛋白表达呈负相关(r=-0.55,P0.01);与模型组相比,二陈汤中剂量组MUC5AC蛋白表达显著减弱,AQP5蛋白表达增强(均P0.01),MUC5AC与AQP5蛋白表达呈负相关(r=-0.75,P0.01)。结论二陈汤对慢性支气管炎气道黏液高分泌有调节作用,其机制可能与抑制MUC5AC、上调AQP5蛋白表达有关。     

辛伐他汀对脂多糖诱导的细胞黏液高分泌的抑制

目的 观察具有抗炎活性的辛伐他汀对脂多糖 (LPS) 诱导的肺泡上皮细胞A549黏蛋白表达的影响并探讨其机制.方法 用不同浓度的辛伐他汀作用于培养的A549细胞,采用定量RT-PCR、ELISA和明胶酶谱法分别检测细胞的黏蛋白MUC5AC mRNA表达水平、MUC5AC蛋白含量及细胞上清基质金属蛋白酶 (MMP)-9活性.结果 辛伐他汀组细胞中MUC5AC蛋白含量及MUC5AC mRNA水平较脂多糖组均明显下降(P<0.05), 且浓度越高,作用越强.在正常情况下A549细胞培养上清液中几乎检测不到MMP-9活性,而LPS作用后上清中MMP-9活性明显增强(P<0.01),预先给予不同浓度辛伐他汀孵育细胞培养上清液MMP-9活性显著下降(P<0.05).结论 LPS诱导的A549细胞黏蛋白MUC5AC在mRNA和蛋白水平的升高与MMP-9活性增强有关,而辛伐他汀可减少LPS诱导的MUC5AC mRNA及蛋白表达,且呈浓度依赖性,提示其作用可能与抑制MMP-9活性有关.     

黏蛋白5AC、黏蛋白6与幽门螺杆菌感染和胃癌的关系

目前越来越多的研究表明,黏蛋白5AC(MUC5AC)、黏蛋白6(MUC6)的表达程度与幽门螺杆菌(Hp)感染和胃癌的发生密切相关,其中MUC5AC、MUC6的基因多态性成为研究热点之一。本文就MUC5AC、MUC6与Hp感染和胃癌的关系作一综述。     

粘蛋白MUC1、MUC2、MUC4和MUC5AC在胰腺导管腺癌中的表达及意义

目的 研究胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDA)组织中粘蛋白MUC1、MUC2、MUC4和MUC5AC的表达及其与临床病理参数间的关系.方法 应用SP免疫组织化学方法检测26例PDA、4例CP、16例正常胰腺组织、2例导管内乳头状黏液性肿瘤(IPMN)、4例实性假乳头状瘤(SPT)和1例浆液性囊性肿瘤(SCN)组织中MUC1、MUC2、MUC4、MUCSAC的表达.结果 正常胰腺和CP组织仅有MUC1表达,表达率均为100%;PDA中MUC1、MUC4和MUC5AC表达率分别为100%、88.5%(23/26)和76.9%(20/26);2例IPMN均见MUC2和MUC5AC表达;SPT和SCN中4种粘蛋白均无表达.MUC4和MUC5AC表达同PDA的临床病理参数之间无相关性(P＞0.05).结论 PDA时存在多种粘蛋白的表达,联合检测MUC1、MUC2、MUC4和MUC5AC的表达可能有助于对PDA的诊断和鉴别诊断.     

Expression of gastric mucin in the stomachs of two patients with Menetrier's disease: an immunohistochemical study

Menetrier's disease is a rare gastric condition characterized by marked proliferation of the mucosa and variable mucus secretion and achlorhydria. We report, for the first time, minor variations in MUC1-7 distribution in the mucosa of two stomachs from patients with Menetrier's disease, when compared with a normal stomach. All stomachs stained positively for MUC4, 5AC and 6 and showed no or little staining with MUC2 and 3. Thus, Menetrier's disease is characterized by an excess quantity of mucus secretion, but differs little from normal stomachs with regards to the types of mucin produced. The mucins, MUC1-7, are found with variable distribution in different body tissues; MUC4, MUC5AC and MUC6 are typically found in gastric mucosa.     

H pylori colocalises with MUC5AC in the human stomach

BACKGROUND: The bacterium Helicobacter pylori is able to adhere to and to colonise the human gastric epithelium, yet the primary gene product responsible as a receptor for its adherence has not been identified. AIMS: To investigate the expression of the gastric mucins MUC5AC and MUC6 in the gastric epithelium in relation to H pylori colonisation in order to examine their possible roles in the binding of H pylori. PATIENTS: Seventy two consecutive patients suspected of having H pylori infection. METHODS: MUC5AC, MUC6, and H pylori were detected in single sections of antral biopsy specimens using immunohistochemical triple staining. RESULTS: MUC5AC was expressed in the superficial epithelium and the upper part of the gastric pits. MUC6 expression was detected in the lower part of the gastric pits. The expression of both mucins in the epithelium was complementary. In each patient, there was a sharply delineated transition between MUC5AC and MUC6 producing cell populations. In all H pylori positive patients there was a striking colocalization of H pylori and MUC5AC; more than 99% of the bacteria were associated with either extracellular MUC5AC or the apical domain of MUC5AC producing cells. CONCLUSIONS: H pylori is very closely associated with extracellular MUC5AC and epithelial cells that produce MUC5AC. This indicates that MUC5AC, but not MUC6, plays a role in the adhesion of H pylori to the gastric mucosa.     

MUC6 down-regulation correlates with gastric carcinoma progression and a poor prognosis: an immunohistochemical study with tissue microarrays

Purpose MUC6 was first discovered by screening a gastric mucosa cDNA library and is expressed in the mucous cells of the neck zone and antral glands of the stomach. The aim of the present study was to clarify whether down-regulation has any clinicopathological or prognostic significance in gastric neoplasia.Methods Expression of MUC6, MUC5AC and MUC2 was examined using tissue microarrays for immunohistochemistry in gastric carcinomas (n = 225), adenomas (n = 40), and normal mucosa (n = 89) and compared with clinicopathological parameters and survival data.Results MUC6 expression was lower in gastric carcinomas than in adenomas or normal mucosa (P < 0.05) and inversely correlated with tumor size, depth of invasion, lymphatic and venous invasion, lymph node metastasis and UICC staging (P < 0.05). Positive links with expression of MUC2 and MUC5AC were noted (P < 0.05). MUC6 expression was lower in diffuse-type than intestinal-type lesions (P < 0.05). Kaplan–Meier analysis indicated that cumulative survival of patients with no MUC6 expression was significantly lower than with weak, moderate or strong expression in all and even advanced gastric carcinoma (P < 0.05). Multivariate analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to concordantly affect the relationship between MUC6 expression and prognosis.Conclusions Down-regulation of MUC6 may contribute to malignant transformation of gastric epithelial cells and underlie the molecular bases of growth, invasion, metastasis and differentiation of gastric carcinoma. Altered expression might therefore be employed as an indicator of pathobiological behaviors and prognosis of gastric carcinoma.     

Effects of Helicobacter pylori infection on mucin expression in gastric carcinoma and pericancerous tissues

BACKGROUND: Helicobacter pylori infection is one of the major causes of human gastric carcinoma and can disturb the gastric mucosa barrier. Mucins have not only lubricating and protecting functions, but are also related to signal transduction, turnover of gastric epithelium and carcinogenesis of gastric mucosa. The aim of this study was to investigate the relationship between H. pylori infection and aberrant mucin expression in patients with gastric carcinoma. METHODS: H. pylori infection was diagnosed by the Warthin-Starry staining method. Different kinds of mucins were detected using an immunohistochemical method. RESULTS: Of 46 patients with gastric carcinoma, there were 26 patients who had H. pylori infection (56.5%). Of 21 pericancerous mucosas from the H. pylori-positive patients, 14 had MUC2 expression (66.7%), seven had strong MUC1 expression (+ + +) (33.7%), seven had strong MUC6 expression (+ + +) (33.3%), and five had strong MUC5AC expression (+ + +) (23.8%). In contrast, only six of 18 H. pylori-negative pericancerous mucosas had MUC2 expression (33.3%) (P < 0.05 compared with H. pylori-positive pericancerous mucosas), 12 had strong MUC1 expression (+ + +) in 16 H. pylori-negative pericancerous mucosas (75%) (P < 0.05), 11 had strong MUC6 expression (+ + +) in 16 H. pylori-negative pericancerous mucosas (68.8%) (P < 0.05), and 10 had strong MUC5AC expression (+ + +) in 14 H. pylori-negative pericancerous mucosas (71.4%) (P < 0.01). Of the H. pylori-positive cancerous tissues, 50% (13/26) had MUC1 expression and 38.5% (10/26) had MUC6 expression. In comparison, of the H. pylori-negative cancerous tissues, 80% (16/20) had MUC1 expression (P < 0.05) and 80% (16/20) had MUC6 expression (P < 0.01). CONCLUSIONS: The results indicate that H. pylori infection can alter the expression of some mucin genes in pericancerous mucosa and cancerous tissues of gastric carcinoma, then destroy the gastric mucosa barrier.     

Mucin gene expression in intestinal epithelial cells in Crohn's disease

BACKGROUND: Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease of unknown origin. It is characterised by chronic mucosal ulcerations which affect any part of the intestine but most commonly are found in the ileum and proximal colon. AIMS: Studies were undertaken to provide information regarding cell specific expression of mucin genes in the ileum of patients with CD. PATIENTS AND METHODS: Expression of mucin genes was analysed in the ileal mucosa of patients with CD and controls by in situ hybridisation and immunohistochemistry. RESULTS: In healthy ileal mucosa, patients with CD showed a pattern identical to normal controls with main expression of MUC2 and MUC3, lesser expression of MUC1 and MUC4, and no expression of MUC5AC, MUC5B, MUC6, or MUC7. In the involved mucosa, the pattern was somewhat comparable although heterogeneous to that observed in healthy ileal mucosa. Importantly, a particular mucin gene expression pattern was observed in ileal mucosa close to the ulcer margins in ulcer associated cell lineage, with the appearance of MUC5AC and MUC6 mRNAs and peptides, which are normally restricted to the stomach (MUC5AC and MUC6) and duodenum (MUC6), and disappearance of MUC2. CONCLUSIONS: Our results suggest that gel forming mucins (more particularly MUC5AC and MUC6) may have a role in epithelial wound healing after mucosal injury in inflammatory bowel diseases in addition to mucosal protection.     

Prognostic Significance of Mucin Expression in Gastric Carcinoma

In patients with gastric carcinomas, the role of the alteration of mucin expression in overall survival has been a matter of some speculation, but few studies have been reported. The aim of our study was to determine the relationship between MUC1, MUC2, and MUC5AC expression and patient survival, with a secondary aim designed to investigate the alteration of MUC expression within various clinicopathologic parameters. Forty-four specimens from gastric carcinoma patients were immunohistochemically evaluated using the monoclonal antibodies for MUC1 (EMA, clone E29), MUC2 (CCP58), and MUC5AC (human gastric mucin, clone 45M1). MUC1 expression increased in gastric carcinoma. MUC1 positivity was determined to be statistically significant, with poor clinicopathological parameters and decreased long-term survival. MUC5AC expression decreased in gastric carcinoma. In addition, patients with MUC5AC-positive tumors also had poor clinicopathological parameters and showed shorter survival than those with MUC5AC-negative tumors. MUC2 expression was not significantly associated with patient survival. We confirmed that the expression of mucins is associated with characteristics of differentiation in gastric carcinoma. Poor patient outcomes were seen in gastric carcinomas with MUC1 mucin expression and MUC5AC positivity.     

The role of mucin in GERD and its complications

Acid, pepsin and other noxious material reach the esophageal mucosa and interact with the luminal aspect of the squamous epithelium. The first protective barrier to these potentially injurious substances is the mucus buffer layer that covers the mucosa. In healthy people, the esophagus has a protective surface adherent mucus gel barrier. Levels of mucin glycoprotein are considerably increased in response to acid and pepsin. A wide spectrum of mucin genes are expressed in normal esophageal mucosa, squamous cell carcinoma of the esophagus, Barrett epithelium and esophageal adenocarcinoma. The mucins MUC5AC and MUC6 are expressed to a similar degree in Barrett metaplasia and gastric mucosa, as is MUC2 in Barrett intestinal metaplasia and small bowel mucosa. Increased expression of MUC1 is associated with progression from dysplasia to adenocarcinoma of the esophagus. Thus, mucins have an important role in the defense of esophageal mucosa against the acid, pepsin and bile that are present in the refluxate. Changes in the expression of mucins occur in patients with GERD, and might lead to the development of new drugs.     

Mucin gene expression in Barrett's oesophagus: an in situ hybridisation and immunohistochemical study

BACKGROUND AND AIMS: Mucin genes are expressed in a site specific manner throughout the gastrointestinal tract. Little is known about the expression pattern in the oesophagus. In this study we have investigated MUC gene expression in both the normal oesophagus and specialised intestinal metaplasia (Barrett's oesophagus). PATIENTS: Archived paraffin embedded material from eight specimens of normal oesophagus, 18 Barrett's oesophagus, eight gastric metaplasia, six high grade dysplasia, and six cases of adenocarcinoma were examined for expression of the mucin genes MUC1-6. METHODS: Mucin mRNA was detected by in situ hybridisation using [(35)S] dATP labelled oligonucleotide probes. Mucin core protein was detected by immunohistochemistry. RESULTS: Normal oesophagus expressed MUC5B in the submucosal glands and MUC1 and MUC4 in the stratified squamous epithelium. Barrett's oesophagus strongly expressed MUC5AC and MUC3 in the superficial columnar epithelium, MUC2 in the goblet cells, and MUC6 in the glands. In high grade dysplasia and adenocarcinoma there was downregulation of MUC2, MUC3, MUC5AC, and MUC6, but upregulation of MUC1 and MUC4 in half of the specimens examined. CONCLUSIONS: Normal oesophagus and Barrett's oesophagus have a novel pattern of mucin gene expression. Barrett's oesophagus expressed the mucins associated with normal gastric epithelium and normal intestinal epithelium. While most mucin genes were downregulated in severely dysplastic and neoplastic tissues, there was upregulation of the membrane bound mucins MUC1 and MUC4. This may prove useful in detecting early signs of progression to adenocarcinoma of the oesophagus.