原发性肝细胞癌中CD44v6和nm23H1基因的转录表达及临床意义

研究CD44v6 mRNA和nm23H1 mRNA表达与肝细胞癌（HCC）侵袭转移和预后的关系。应用原位杂交方法，检测分析HCC组织中CD44v6 mRNA和nm23H mRNA表达。99例HCC中，CD44v6 mRNA和nm23H1 mRNA表达阳性率分别为41．4％和76．8％。CD44v6mRNA表达与nm23H1mRNA表达呈负相关。CD44v6和nm23HmRNA表达均与HCC侵袭转移倾向和预后相关。检测CD44v6和nm23H1表达有可能成为HCC 侵袭转移和预后判断的病理生物学指标。     

胆囊癌组织中CD44v6和nm23的表达及其意义

目的研究胆囊癌组织中CD44v6、nm23蛋白表达及意义和两者之间的关系。方法用免疫组化的方法检测 36例胆囊癌和27例癌旁上皮组织中CD44v6和nm23蛋白的表达。结果胆囊癌组织中CD44v6和nm23的阳性率分别为41.7％和72.2％,均与癌旁上皮的阳性率有显著性差异:CD44v6的表达与胆囊癌的淋巴结转移呈正相关,而与组织学类型、临床分期无关;nm23的表达与胆囊癌的淋巴结转移、临床分期呈负相关,而与组织学类型无关。CD44v6和nm23蛋白的表达呈负相关。结论 CD44v6和nm23蛋白可能在胆囊癌的形成、淋巴结转移和病程进展等方面起着重要作用,且两者呈互相拮抗的关系,可作为判断胆囊癌侵袭和淋巴结转移的标记物。     

CD44v6在胃癌胃镜标本和术后标本中的表达及与胃癌生物学行为的关系

目的:研究CD44v6在胃癌胃镜标本和术后标本中的表达,并分析其与胃癌生物学行为的关系.方法:随机选取辽宁医学院附属第二医院普通外科2004-2009年收治的有详细病例资料的胃癌患者50例,应用免疫组织化学方法检测胃镜标本和术后标本胃组织中CD44v6的表达.结果:CD44v6在胃癌胃镜标本、术后标本和转移淋巴结中的表达率分别为60.00%、64.00%、80.77%.显著高于胃良性病变(P＜0.01);CD44v6在肠型胃癌中的表达率显著高于弥漫型胃癌(75.86% vs 47.62%,P＜0.05).胃癌胃镜和术后标本中CD44v6的表达与胃癌浸润深度,TNM分期和淋巴结转移均有关(P＜0.05).CD44v6在胃癌胃镜标本和术后标本中的总体表达率无显著性差异(P＞0.05);相同临床病理参数,CD44v6在胃癌胃镜标本和术后标本中的表达率无显著性差异(P＞0.05).结论:CD44v6可作为术前预测胃癌的发生、病期进展和转移潜能的辅助生物学指标之一.     

肝细胞癌p53及nm23-H1 mRNA表达的意义

目的探讨ｐ５３,ｎｍ２３Ｈ１与原发性肝细胞癌（ＨＣＣ）发生发展的关系．方法运用原位分子杂交技术对４９例ＨＣＣ中ｐ５３和ｎｍ２３Ｈ１基因ｍＲＮＡ进行检测,并结合临床病理特征进行分析．结果ｐ５３ｍＲＮＡ杂交阳性２３例,占４６９％;ｐ５３ｍＲＮＡ过表达与肿瘤的肝内转移．包膜侵犯及Ｅｄｍｏｎｄｓｏｎ分级相关（Ｐ＜００５）;ｎｍ２３Ｈ１ｍＲＮＡ阳性表达２７例,占５５１％;ｎｍ２３Ｈ１ｍＲＮＡ表达与肿瘤肝内转移及ＴＮＭ分期呈负相关（Ｐ＜００５）;同时发现ｐ５３ｍＲＮＡ过表达和ｎｍ２３Ｈ１ｍＲＮＡ低表达在ＨＣＣ肝内转移中具有协同作用．结论ｐ５３和ｎｍ２３Ｈ１参与ＨＣＣ的发生发展,ｐ５３过表达及ｎｍ２３Ｈ１低表达提示ＨＣＣ肝内转移．     

黏附分子CD44的表达及其糖基化与肝癌转移的相关性

目的 探讨CD44S及其变异体CD44v分子的表达和其糖基化与肝癌细胞侵袭转移的关系. 方法 用免疫组织化学法、量子点、RT-PCR、Western blot、细胞免疫荧光染色、甲基化特异性聚合酶链反应等技术检测转移与非转移性肝癌组织、不同转移潜能人肝癌细胞株中CD44S及其变异体CD44v的定位与表达;并应用多重凝集素印迹法检测这些细胞株中CD44v6的糖基化差异.组间均数比较应用方差分析及t检验,多组间等级资料的比较采用Wilcoxon秩和检验,各组间率的比较采用x2检验.结果 免疫组织化学结果显示,CD44S蛋白定位以细胞质为主; CD44v3、CD44v4/5蛋白定位于细胞膜与细胞质;而CD44v6主要定位于细胞膜.组织芯片结果显示,相对于CD44S及其他CD44v,CD44v6在转移组的表达水平高于非转移组(阳性率为75％与46％),差异具有统计学意义(x2=8.828,P＜0.05);量子点检测(t=2.392,P＜0.05)与血清学检测(t=2.56,P＜0.05)也证实这一结果.Western blot结果显示,CD44v6的表达与肝癌细胞转移潜能呈正相关.此外,在MHCC97L、MHCC97H肝癌细胞中CD44v6基因启动子发生不完全甲基化,而在Hep3B细胞中则发生完全甲基化.而且,相对于Hep3B细胞,MHCC97L及MHCC97H细胞中CD44v6蛋白对朝鲜槐凝集素、黑接骨木凝集素及麦胚凝激素的亲和力较高. 结论 在CD44S及其变异体CD44v中,CD44v6蛋白的高表达与肝癌转移潜能的增强呈正相关;其高表达可能与基因启动子低甲基化有关.此外,CD44v6蛋白唾液酸寡糖链的增加可能与肝癌细胞转移潜能增高有关.     

Nm23-H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma

Abstract: Aims/Background: Decreased expression of nm23, a putative metastasis suppressor gene, has been reported to be related to either intrahepatic metastasis or a poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the true role of nm23-H1 expression in both intrahepatic and distant metastases of HCC. Methods: Thirteen patients with single-nodule HCC, seven patients with HCC having satellite nodules and seven patients with HCCs having extrahepatic metastases were included in this study. The expression of nm23-H1 protein was immunohistochemically examined in both primary and metastatic nodules. Results: Ten of 13 single-nodule HCCs were found to overexpress nm23-H1 protein. All main tumors, having satellite nodules, were found to overexpress nm23-H1 protein, except for two HCCs, which only partially expressed nm23-H1 protein. Regarding the nm23-H1 expression in intrahepatic metastases, most nodules overexpressed the protein. The expression of nm23-H1 was found to be low in only one intrahepatic metastasis specimen, while its primary tumor was also found to show a low expression of nm23-H1 protein. Microscopic portal vein invasion was found in three of the five patients studied, and all cancer cells in portal invasion overexpressed nm23-H1 protein. Nm23-H1 protein was expressed in all distant metastatic tumors and the staining intensity of most metastatic nodules was similar to that of the primary tumors. Conclusions: Our study demonstrated that nm23-H1 expression did not always decrease but instead tended to increase at both intrahepatic and extrahepatic metastatic sites. Based on these findings, nm23-H1 expression is not considered to be a reliable indicator of either intrahepatic or distant metastasis in HCC.     

CD44v6及nm23-H1表达与肝细胞癌侵袭转移

目的原位检测肝细胞癌(HCC)中CD44v6 mRNA及nm23-H1 mRNA的表达,了解CD44v6 mRNA及nm23-H1 mRNA的表达与HCC侵袭转移的关系,了解HCC中CD44v6 mRNA表达与nm23-H1 mRNA表达的相关性.方法采用PCR法合成CD44v6 cDNA探针,体外转录法合成nm23-H1 cRNA探针,采用原位杂交法检测HCC 33例 CD44v6 mRNA和nm23-H1 mRNA的表达.结果侵袭转移倾向高危组的10例HCC标本中,CD44v6 mRNA和nm23-H1 mRNA的阳性率分别为80.0%(8/10)和40.0%(4/10);侵袭转移倾向低危组的23例HCC标本中,CD44v6 mRNA和nm23-H1 mRNA的阳性率分别为21.7%(5/23)和91.3%(21/23).CD44v6 mRNA的表达与HCC的侵袭转移倾向具有正相关性(P＜0.01),nm23-H1 mRNA的表达与HCC的侵袭转移倾向具有负相关性(P＜0.01),CD44v6 mRNA及nm23-H1 mRNA的表达具有负相关性(P＜0.01).结论检测CD44v6 mRNA及nm23-H1 mRNA的表达可能成为HCC转移预后判断的指标.     

明胶酶、CD44v6在结直肠癌中的表达及意义

目的探讨明胶酶在结直肠癌中的表达及其CD44v6在结直肠癌侵袭转移过程中的关系。方法采用明胶酶谱（gel zymography）和S-P免疫组化对50例结直肠癌癌组织和相应正常组织中的明胶酶、CD44v6进行检测。结果明胶酶在结直肠癌中的表达水平显著高于正常组织（P〈0．05）；明胶酶与结直肠癌的Duke’s分期呈同步的正相关（P〈0．05）；明胶酶在CD44v6强阳性组中表达量升高显著（P〈0．05）。结论明胶酶与结直肠癌的侵袭转移性有着密切的关系，不仅在癌细胞的酶解，而且在癌细胞的黏附、运动过程中有可能发挥着重要作用。     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.     

Expression of nm23 gene in hepatocellular carcinoma tissue and its relation with metastasis

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CD15、CD44v6和CD54检测与肝癌复发转移的关系研究

探讨粘附因子CD15、CD44v6和CD54（ICAM-1）在肝细胞癌中的表达及临床意义。利用免疫组织化学染色对51例肝癌手术切除石蜡包埋标本进行CD15、CD44V6、CD54的检测。并结合临床病理指标（Edmondson分级、侵袭转移倾向）进行分析。CD15、CD44v6和CD54在侵袭转移倾向高危组中分别为40%、45%、55%,在低危组中分别为13%、19%、19%;CD15、CD44v6和CD54在HCCⅡ级中分别为10%、20%、20%,在IV级中分别30%、50%、50%。结论：CD15、CD44v6和CD54的异常表达与HCC分期和侵袭转移有关;利用CD15、CD44v6和CD54等预测肝癌的复发转移有可能是一种新的途径。     

胃癌组织α-连环素和CD44v6表达的检测和意义

目的 研究胃癌组织和癌旁正常胃黏膜组织α-连环素和CD44v6的表达，以探讨它们的表达异常与胃癌病人的临床和病理特征的关系。方法采用免疫组化的方法半定量地检测胃癌组织和胃癌的癌旁正常黏膜这两种细胞黏附分子的表达情况并将二者的表达情况和胃癌病人的临床和病理特征进行比较。结果部分胃癌组织中α-连环素表达减少或消失，而在正常黏膜中α-连环素均正常表达。α-连环素的表达异常与胃癌病人的性别、年龄、胃癌的部位无明显相关性（P〉0．05），与胃癌组织的病理分级及远处转移有相关性（P〈0．05）。在正常胃黏膜中CD44v6无表达，而在部分胃癌组织中CD44v6呈阳性表达，二者差异具有显著性（P〈0．005）。CD44v6的表达上调与胃癌病人的性别、年龄、胃癌的部位及病理分级无明显厢关性（P〉0．05），与理处转移呈正相关（P〈0．05）。胃癌组织中α-连环素和CD44v6的表达呈负相关（P〈0．05）。结论胃癌组织中α-连环素和CD44v6有异常表达；胃癌的远处与原转移发肿瘤组织中α-连环素和CD44v6的异常表达有关；α-连环素和CD44v6的异常表达参与了肿瘤的转移过程。     

骨桥蛋白和CD44v6在肝癌中的表达及意义

骨桥蛋白(osteopontin，OPN)是一种分泌型钙结合磷酸化糖蛋白，其中含有特异的与细胞黏附有关的RGD(Arg-Gly-Asp)序列，通过与其受体整合素、CD44等结合来促进细胞的趋化、黏附和迁移，从而介导肿瘤细胞的侵袭转移，在肿瘤的复发与转移中起到重要作用。OPN过表达与肝癌的复发和转移有关，并认为是早期预测肿瘤复发的一个指标。现对OPN和CD44v6在肝癌中的表达进行研究，以了解其临床意义。     

结直肠癌组织中CD44V3,v6蛋白的表达意义

目的研究CD44v3,v6蛋白在结直肠癌组织中的表达及其预后意义.方法应用EnvisionTM免疫组化法,回顾性分析121例结直肠癌石蜡组织CD44v3,v6的表达.患者中位随访时间为67.77mo.结果CD44v3,v6在结直肠癌中的阳性率分别为60.3%和57.9%.CD44v3的阳性表达与患者肿瘤部位,淋巴结转移状况、远处转移与否、临床分期密切相关(P＜0.05,Spearman等级相关检验).CD44v6的阳性表达与患者性别、淋巴结转移状况、远处转移与否、临床分期密切相关(P＜0.05,Spearman等级相关检验).Kaplan-Meier生存曲线,Log-rank检验单因素生存分析结果显示,CD44v3阴性、阳性患者的五年生存率分别为81.25%,60.27%,两者之间存在显著性差异(P=0.035);CD44v6阴性、阳性患者的5 a生存率分别为80.39%,60.00%,两者之间亦存在显著性差异(P=0.0299).Cox模型多因素生存分析结果显示,CD44v3表达是影响结直肠癌预后的独立因素.结论CD44v3,v6蛋白与结直肠癌转移、预后相关,CD44v3是影响结直肠癌预后的独立因素.     

胃癌患者血清及癌组织中CD44v6表达及意义

[目的]检测胃癌患者血清及胃癌组织中CD44v6的表达及其与胃癌临床病理特征间的关系,进一步阐述CD44v6在胃癌发生发展中的作用。[方法]收集40例经病理证实的胃癌患者,20例正常健康体检者为对照组,20例取自距癌组织边缘5cm以上癌旁胃黏膜标本。采用双抗体夹心-酶联免疫吸附法检测40例胃癌患者术前和20例正常健康者血清中CD44v6水平,免疫组化SP法测定40例经手术切除的胃癌组织标本和20例癌旁胃黏膜标本中CD44v6的表达。[结果]①胃癌患者血清中CD44v6[(177.21±46.48)μg/L]高于正常健康者(P<0.01)。②癌组织中CD44v6的阳性表达率为77.5%,显著高于癌旁胃黏膜中的表达(P<0.01),CD44v6在血清和组织中的表达随组织学分级、临床分期的增高及有无淋巴结转移而升高,呈正相关性。[结论]CD44v6参与了胃癌的发生,并且可反映机体肿瘤的负荷状态及预测肿瘤的进展;检测CD44v6的血清含量可能为胃癌的诊断提供依据。     

The expression and clinical significance of CD44v in human gastric cancers

INTRODUCTION CD44 was originally implicated as a "homing"receptor directing the migration of recirculating lymphocytes[1]. CD44 expression has been confirmed not only in lymphocytes but also in a wide variety of epithelial tissues. It is considered as an important cell adhesion molecule for cell to cell interactions[2].