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1.
N-acetylglucosaminyltransferase-V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagines (N)-linked oligosaccharides of cell proteins. We examined the implication of GnT-V and beta1-6 branching N-linked oligosaccharide expression in human testicular germ cells during malignant transformation and cancer progression. We analyzed immuhistochemically orchiectomy specimens of 130 patients with testicular germ cell tumors (TGCT) using anti-GnT-V monoclonal antibody, and compared GnT-V expression with clinicopathological features. N-linked oligosaccharide structural analysis was also performed to confirm the oligosaccharide profile produced by GnT-V. GnT-V was positive in all normal testis samples. This positive incidence declined in TGCT according to clinical stage; 16/71 (22.5%) in stage I, and 3/59 (5.1%) in stage II/III (p=0.015, chi(2) test). When divided into pathological subtypes, GnT-V positive incidences in stage I seminoma, stage II/III seminoma, stage I non-seminomatous germ cell tumor (NSGCT), and stage II/III NSGCT were 3/43 (7%), 0/22 (0%), 13/28 (46.4%), and 3/37 (8.1%), respectively. In stage I NSGCT, patients with GnT-V-negative tumor samples were at a significantly higher risk of recurrence than those with GnT-V-positive tumors (p=0.015, log-rank test). N-linked oligosaccharide structural analysis revealed that a normal testis has three kinds of beta1-6 branching N-linked oligosaccharides, all of which are downregulated in TGCT tissues. These results suggest that GnT-V and beta1-6 branching N-linked oligosaccharide expressions are downregulated during carcinogenesis and progression of human TGCT. GnT-V may be a promising recurrence predictor for stage I NSGCT.  相似文献   

2.
N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyses beta1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cell proteins. The present study aimed to investigate GnT-V expression and its prognostic significance in endometrial cancer. N-acetylglucosaminyltransferase V expression was studied by immunohistochemistry in 74 surgically resected endometrial cancers, and the staining intensity was evaluated. High GnT-V expression in tumour cells was found in 43 (58.1%) of the 74 cases, and was positively correlated with advanced patient age, histological grade, and lymph vascular space involvement. Patients with high GnT-V expression had significantly impaired overall survival and progression-free survival (PFS) (P=0.0041 and P=0.0023, respectively) compared to patients with low expression of GnT-V. On multivariate analysis, GnT-V expression was an independent prognostic factor for PFS (P=0.0364). beta1-6 branching of asparagine-linked oligosaccharides was also detected in GnT-V-positive endometrial cancer cells by leukoagglutinating phytohaemagglutinin (L(4)-PHA) staining, and the molecular size of the major glycoproteins recognised by L(4)-PHA was approximately 60-200 kDa by lectin blot analysis. These results suggested that high GnT-V expression was correlated with an unfavourable clinical outcome, and that GnT-V is involved in the malignant potential of endometrial cancer by increasing the synthesis of beta1-6 branching of asparagine-linked oligosaccharides.  相似文献   

3.
N-Acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes beta 1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cell proteins. Metastatic potential of various cancer cells has been shown to correlate with increase of GnT-V activity and concomitant beta 1-6 branching of N-acetylglucosamine. However, protein expression of GnT-V in human cancer tissue and its clinical significance have not yet been demonstrated. To clarify the possible relationship between metastasis and GnT-V in human colorectal cancer, protein expression of GnT-V was studied using surgically resected specimens. We established a monoclonal antibody against GnT-V and performed immunohistochemical analysis of 103 human colorectal cancer cases. Of 103 cases, 26 cases (25.2 %) showed specific expression of GnT-V in colorectal cancer tissues. The expression of GnT-V was significantly correlated with distant metastasis (P < 0.05, chi2 test). Overall 5-year survival rate was 52.8% for GnT-V-positive patients and 81.7% for GnT-V-negative patients (P < 0.01, Log-rank test). We showed direct evidence for the relationship between GnT-V and metastasis in human colorectal cancer. Screening of GnT-V expression in colorectal cancer may provide useful information for prognosis of postoperative patients.  相似文献   

4.
PURPOSE: N-Acetylglucosaminyltransferase V (GnT-V), a key enzyme in the formation of branching of asparagine-linked oligosaccharides, is strongly linked to tumor invasion and metastasis of colon and breast cancers. However, GnT-V is expressed in many tissues, including normal lung. GnT-V expression has not been examined previously in human lung cancers. The objective of this study is to examine GnT-V expression in non-small cell lung cancers (NSCLCs) and to determine its relationship to biological and clinicopathological characteristics and prognosis. EXPERIMENTAL DESIGN: GnT-V expression was studied by immunohistochemistry in 217 surgically resected NSCLCs and analyzed statistically in relation to various characteristics. RESULTS: High GnT-V expression was found in 113 (52.1%) NSCLCs, and low GnT-V expression was found in 104 (47.9%) NSCLCs. Multivariate logistic regression analysis revealed a significant association between low GnT-V expression and squamous cell carcinomas, as compared with nonsquamous cell carcinomas (P = 0.02). Among biological characteristics of tumors, Ki-67 labeling index was higher in tumors with low GnT-V expression than in those with high GnT-V expression, although this difference was not statistically significant (P = 0.09). Patients with tumors having low GnT-V expression had significantly shorter survival time than patients with tumors having high GnT-V expression in 103 patients with pStage I NSCLCs (5-year survival rates, 49% and 86%, respectively; P = 0.0009), as well as in 59 patients with pStage I non-squamous cell carcinomas (5-year survival rates, 54% and 89%, respectively; P = 0.007). Low GnT-V expression was a significant unfavorable prognostic factor in pStage I NSCLCs (hazard ratio, 2.86; P = 0.002) and in pStage I nonsquamous cell carcinomas (hazard ratio, 3.02; P = 0.02). Furthermore, beta1-6 branching of asparagine-linked oligosaccharides, which are products of GnT-V, were increased highly or moderately in 8 of 10 tumors with high GnT-V expression, as judged by leukoagglutinating phytohemagglutinin staining. CONCLUSIONS: GnT-V expression is associated with histology in NSCLCs. Low GnT-V expression is associated with shorter survival and poor prognosis in pStage I overall NSCLCs and non-squamous cell carcinomas.  相似文献   

5.
6.
Cell surface sialylation and beta1-6 branching of L-PHA reactive oligosaccharides play an important role in metastatic capacities of various tumor cell lines. We analyzed the expression and sialylation of L-PHA reactive oligosaccharides in human diffuse large B cell lymphoma (DLBCL). DLBCL was grouped into three types; i). Group A, non-reactive type with no expression of L-PHA reactive oligosaccharides, ii). Group B, sialylated type with expression of sialylated L-PHA reactive oligosaccharides and iii). Group C, non-sialylated type with expression of non-sialylated L-PHA reactive oligosaccharides. To clarify the linkage of sialic acid residues in L-PHA reactive oligosaccharides of Group B cases, L-PHA lectin histochemistry after treatment with two different neuraminidases was performed. In all Group B cases, L-PHA binding reactivity was found after treatment with Vibrio cholerae neuraminidase. But not after treatment with Newcastle disease virus neuraminidase. These data indicate that alpha2,6-linked sialic acid residues were predominantly involved in sialylation of L-PHA reactive oligosaccharides of Group B. To clarify the relationship between expression of N-acetylglucosaminyltransferase V (GnT-V), which catalyzes beta1-6 branching of L-PHA reactive oligosaccharides, and L-PHA reactivities in DLBCL, we investigated the expression of GnT-V using immunohistochemical methods. Most of the Group B and C cases expressed GnT-V while 33% of Group A cases showed no expression of GnT-V. These data suggest that expression of GnT-V is not always correlated with the expression of L-PHA reactive glycoconjugates. Furthermore, survival of patients in Group A which showed no expression of GnT-V was significantly shorter than that of patients in Group C which expressed GnT-V. Therefore, loss of non-sialylated L-PHA reactive oligosaccharides due to lack of expression of GnT-V in lymphoma cells may be associated with aggressiveness of DLBCL.  相似文献   

7.
OBJECTIVE: N-Acetylglucosaminyltransferase V (GnT-V) is a key enzyme in the formation of branching asparagine-linked oligosaccharides and is linked to tumor invasion and metastasis in colon and breast cancers. In normal esophageal epithelium, beta1,6-branched asparagine-linked oligosaccharides synthesized by GnT-V are seen in the basal cell layers but not in the superficial cell layers, and its presence has been shown in invasive esophageal cancers. However, neither GnT-V expression nor its clinical significance has been previously examined in human normal, premalignant and malignant esophageal tissues. METHODS: GnT-V expression was studied by immunohistochemistry using a specific monoclonal antibody in 121 surgically resected specimens of esophageal squamous cell carcinomas (SCCs) and adjacent tissues, and was analyzed statistically in relation to various characteristics. RESULTS: GnT-V expression was observed in none (0%) of the 19 normal epithelial tissues, 1 (2%) of the 43 hyperplastic tissues, 30 (54%) of the 56 mildly dysplastic tissues, 27 (63%) of the 43 moderately dysplastic tissues, 21 (44%) of the 48 in situ SCCs and 29 (26%) of the 110 invasive SCCs (p<0.005). GnT-V expression was observed significantly more frequently in mildly and moderately dysplastic tissues when compared with normal epithelial and hyperplastic tissues (p<0.005), and its frequency was decreased in in situ and invasive SCCs (p<0.005). GnT-V expression was frequently observed in SCCs of small size and without distant metastasis or lymph node metastasis. CONCLUSIONS: Increased expression of GnT-V is associated with the early event of esophageal tumorigenesis.  相似文献   

8.
9.
目的 研究Krüppel样因子17(Krüppel-like factor 17, KLF17)在结直肠癌组织中的表达及其与患者临床病理特征及预后的关系。方法 收集武汉市第一医院128例结直肠癌患者的临床病理资料,采用免疫组织化学法检测KLF17在结直肠癌及对应的非癌结直肠黏膜组织中的表达,Kaplan-Meier法绘制生存曲线,Cox比例风险模型进行生存分析。结果 128例结直肠癌中,83例癌组织存在KLF17低表达。KLF17低表达与结直肠癌患者淋巴结转移相关(P=0.012)。KLF17低表达患者5年无病生存率及总生存率分别为46.3%和49.3%,明显低于KLF17高表达患者的78.3%和82.0%(P均=0.001)。Cox 模型分析结果显示:KLF17、术前肠梗阻、肿瘤分化程度和病理学N分期是结直肠癌患者无病生存时间及总生存时间的独立预后因素(P均<0.05)。结论 KLF17低表达与结直肠癌淋巴结转移相关,是结直肠癌患者预后不良的一个潜在分子指标。  相似文献   

10.
EZH2 和PTEN在膀胱癌的表达及预后分析   总被引:2,自引:1,他引:1       下载免费PDF全文
目的:研究膀胱癌组织EZH2 和PTEN基因的表达,探讨其与膀胱癌临床病理特征及无瘤生存的关系。方法:制作80例膀胱移行细胞癌和10例正常膀胱黏膜(对照组)组织芯片,应用免疫组织化学方法检测EZH 2 和PTEN蛋白的表达,采用Kaplan-Meier 单因素和Cox 比例风险模型多因素分析其与膀胱癌无瘤生存的关系。结果:膀胱癌组织中EZH 2 和PTEN阳性表达率分别为80.0% 和45.0% 。EZH 2 和PTEN的阳性表达率在膀胱癌不同临床分期及病理分级组间存在显著性差异(P<0.05),且两者的表达呈负相关(P=0.033)。 全组膀胱癌患者术后平均无瘤生存期为39.4 个月,1、3、5 年无瘤生存率分别为70.0% 、55.2% 、41.4% 。单因素分析表明:病理分级、肿瘤数目和EZH 2 表达为影响膀胱癌预后的相关因素;多因素分析表明:病理分级、肿瘤数目和EZH 2 表达是膀胱癌复发的独立危险因素。结论:EZH 2 和PTEN异常表达与膀胱癌的发生、发展关系密切。病理分级、肿瘤数目和EZH 2 是膀胱癌预后的独立危险因素。  相似文献   

11.
Previous reports have suggested that changes in oligosaccharide structures, especially beta1-6 branching in N-glycans, which are biosynthesized by UDP-N-acetylglucosamine:alpha mannoside beta1,6 N-acetylglucosaminyltransferase (GnT-V), are linked to tumor metastasis and invasion. In the present study, we investigated GnT-V expression in human hepatocellular carcinoma (HCC) tissues. High expression of GnT-V mRNA was observed in both HCC and the surrounding tissues but not in normal liver. Immunohistochemical study using a newly established monoclonal antibody against GnT-V revealed that positive staining of GnT-V was observed in 75% of HCC tissues and 60% of surrounding tissues and that liver cirrhosis showed much stronger staining of GnT-V than chronic hepatitis without liver cirrhosis (p = 0.0035). In contrast, all of 12 cases of atypical adenomatous hyperplasia diffusely expressed GnT-V. beta1-6 branching in N-glycans, products of GnT-V, was increased in HCC tissues with high expression of GnT-V, as judged by lectin blotting. Levels of GnT-V expression in HCC tissues were positively correlated with a low Ki-67 labeling index (p = 0.0009), small size (p < 0.0001), poor differentiation (p < 0.0001) and absence of portal invasion (p = 0.018). Furthermore, HCC cases with low or no expression of GnT-V were more likely to show recurrence than cases with high expression (p = 0.0373). These findings strongly suggest that GnT-V expression is concerned mainly with an early phase of hepatocarcinogenesis.  相似文献   

12.
Background: Generally, little is known about prognostic factors in bladder cancer patients under 40 years of age. We therefore performed a retrospective study to identify prognostic factors in these younger bladder cancer patients. Methods: We collected clinicopathological data on bladder cancer patients ≤40 years old diagnosed between 1975 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. Survival curves were generated using the Kaplan–Meier method, and the differences between groups were analyzed using the log-rank test. Univariate and multivariate Cox hazards regression analyses were performed to define hazard ratios (HRs) for cancer-specific survival (CSS). Results: There were statistical differences in race, histological type, cancer stage, tumor size, and surgery treatment groups between overall survival and CSS. Only tumor size and cancer stage were significant independent prognostic risk factors in younger bladder cancer patients for the prediction of CSS. Conclusion: Tumors greater than 30 mm in size and a more advanced stage of bladder cancer were indicative of a poor prognosis in bladder cancer patients ≤40 years old, and long-term follow-up is suggested.  相似文献   

13.
目的:探讨miRNA-203表达水平对结直肠癌患者预后的预测价值。方法:回顾性选择2010年1月至2013年12月来我院接受手术切除治疗的结直肠癌患者120例,所有患者均经病理确认。根据结直肠癌组织中miRNA-203表达水平将患者分为miRNA-203低表达组(n=42)和miRNA-203高表达组(n=78)。分析结直肠癌组织中miRNA-203表达水平与临床病理特征的关系,应用单因素、多因素非条件Cox回归分析影响结直肠癌患者预后的危险因素,并采用Kaplan-Meier法绘制累积生存曲线。结果:结直肠癌患者组织中miRNA-203表达量与年龄、性别、吸烟史、嗜酒史、组织类型、肿瘤位置、肿瘤直径无关(P>0.05),与分化程度、TNM分期、淋巴结转移、脉管浸润有关(P<0.05)。单因素、多因素Cox回归分析结果显示,分化程度为高分化、TNM分期为IV期、组织中miRNA-203低表达是影响结直肠癌患者无进展生存率和总生存率的危险性因素(P<0.05)。Kaplan-Meier法生存曲线结果显示,miRNA-203高表达组结直肠癌患者无进展生存率和总生存率显著高于低表达组(P<0.05)。结论:miRNA-203表达水平可作为预测结直肠癌患者预后的指标。  相似文献   

14.
目的:探讨肌层浸润性膀胱癌根治术预后相关因素。方法:回顾性分析156例腹腔镜下根治性膀胱全切除术及盆腔淋巴结清扫术后肌层浸润性膀胱癌患者生存数据,选择17种可能对预后产生影响的因素,采用Kaplan-Meier法及Cox比例风险模型统计分析。结果:单因素分析示年龄、肿瘤T分期、有无淋巴结转移、肾积水、是否侵犯输尿管下段、是否侵犯淋巴脉管、是否行新辅助化疗、术后辅助放化疗对患者预后的影响差异有统计学意义(P<0.05)。多因素分析示年龄(P<0.001)、肿瘤T分期(P=0.003)、淋巴结转移(P=0.031)、新辅助化疗(P=0.015)为肌层浸润性膀胱癌根治术预后影响因素。结论:年龄、肿瘤T分期、淋巴结转移为影响肌层浸润性膀胱癌根治术患者生存的独立危险因素。新辅助化疗是肌层浸润性膀胱癌根治术预后保护因素。  相似文献   

15.
目的:探讨结肠癌患者外周血中microRNA-630(miR-630)的表达,进一步分析其表达对评估结肠癌进展及预后的价值。方法:使用实时荧光定量PCR(Real time PCR)检测55例结肠癌及21例正常对照者外周血中miR-630的表达,采用统计学方法分析miR-630在结肠癌外周血中的表达及其与肿瘤进展和预后的关系。结果:分析Real time PCR检测结果发现,结肠癌患者外周血中miR-630的表达显著高于正常对照(P<0.05),外周血中miR-630表达与结肠癌的侵袭、转移和分期显著相关(P<0.05),单因素和多因素生存分析发现外周血中miR-630的表达上调与结肠癌预后不良显著相关(P<0.05)。结论:结肠癌患者循环miR-630表达显著上调,与结肠癌侵袭和转移密切相关,并可作为结肠癌的独立预后标记分子。  相似文献   

16.
PURPOSE: RhoGDI2 was recently shown to be a metastasis suppressor gene in models of bladder cancer. We sought to further understand its importance in human cancer by determining the level of its expression and the distribution of its encoded protein in normal human tissues and cell lines and to evaluate whether its protein expression is a determinant of human bladder cancer progression. EXPERIMENTAL DESIGN: RhoGDI2 mRNA and protein expression was evaluated in cell lines and human tissues using Affymetrix and tissue microarrays, respectively. Tissue microarrays represented most human normal adult tissues and material from 51 patients that had undergone radical cystectomy for bladder cancer. In these 51 patients, the chi(2) test was used to test for associations between RhoGDI2 and stage, grade of urothelial carcinoma, histological type, and disease-specific survival status. Cox proportional hazards regression analyses were used to estimate the effect of RhoGDI2 expression level on time to development of metastatic disease and disease-specific survival time, adjusting for grade, stage, and histological type. RESULTS: In normal tissues, there was strong RhoGDI2 protein expression in WBCs, endothelial cells, and transitional epithelium. RhoGDI2 mRNA expression was inversely related to the invasive and metastatic phenotype in human bladder cancer cell lines. In patients with bladder cancer, univariate analysis indicated that reduced tumor RhoGDI2 protein expression was associated with a lower actuarial 5-year disease-free and disease-specific survival (P = 0.01). In addition, patients with tumors that had low or absent RhoGDI2 had a shorter time to disease-specific death (P 相似文献   

17.
Changes in the expression of glycosyltransferases that branch N-linked glycans are associated with many physiological and pathological events, such as cell adhesion, migration, proliferation and tumor cell malignancy. Here, the altered levels of N-acetylglucosaminyltransferase V (GnT-V) and its product β(1,6)-linked GlcNAc in monocytes were observed during inflammation. The effects of GnT-V and aberrant N-linked β(1,6) branching on monocyte adhesion through vascular endothelium and transmigration were investigated. During IFN-γ-induced inflammation, adhesion and transendothelial migration of THP-1 monocytes were enhanced, and the levels of GnT-V and β(1,6)-linked GlcNAc in THP-1 monocytes were significantly decreased. Expression of the GnT-V shRNA vector in THP-1 cells reversed the abnormal IFN-γ-induced characteristics, indicating direct involvement of N-glycosylation in these biological effects. The enhanced adhesion and transendothelial migration were significantly inhibited by functional blockade with antibodies against integrin α5 or β1 in IFN-γ-induced and GnT-V knockdown THP-1 cells, demonstrating the involvement of integrin α5β1 in the monocyte-endothelium interaction. However, IFN-γ treatment and GnT-V knockdown in THP-1 cells lowered expression of N-linked β(1,6) branching on integrin α5 and β1, without affecting the total protein expression of the subunits. Decreased GnT-V expression caused marked enchancement of integrin-induced phosphorylation of focal adhesion kinase (FAK). The augmented FAK-mediated ERK phosphorylation and activation were observed in IFN-γ-induced THP-1 cells. Furthermore, ERK inhibitor pre-treatment nearly abrogated the highly elevated IFN-γ-induced monocyte adhesion and transmigration, concomitant with reversal of the decrease in GnT-V and β(1,6) branching. Our results demonstrate for the first time that decreased GnT-V activity due to inflammatory cytokine induction in human monocytes resulted in enchancement of integrin α5β1-dependent monocyte-vascular endothelium adhesion and transmigration. Consequently, the activation of integrin caused elevation of FAK phosphorylation. These effects promoted FAK-mediated downstream signaling, including the ERK pathway, and indicate that GnT-V may be a potential therapeutic target for vascular inflammatory conditions.  相似文献   

18.
Expression of HIF-1alpha and Glut-1 in human bladder cancer   总被引:3,自引:0,他引:3  
HIF-1 is a heterodimer consisting of the HIF-1alpha and HIF-1beta subunits, and HIF-1alpha is the unique oxygen regulated subunit that determines HIF-1 activity. HIF-1alpha upgrades many gene products which include the glucose transporter protein 1 (Glut-1). Immunohistochemical studies using a monoclonal antibody specific for HIF-1alpha indicate that the overexpression of HIF-1alpha occurs in the most common forms of human cancer, including bladder cancer. The expression of Glut-1 in human bladder cancer is associated with poor prognosis and a low survival rate. To our knowledge, this is the first study to compare the expression of both HIF-1alpha and Glut-1 with clinicopathological characteristics in superficial and invasive human bladder cancer (all invasive bladder cancer patients received radical radiotherapy). The Kaplan-Meier survival analysis curve shows a significant association of HIF-1alpha expression with recurrence and survival in superficial bladder cancer and shows a significant association of Glut-1 with survival in invasive bladder cancer [chi2 (4)=10.52; Pr >chi2 =0.0012].  相似文献   

19.
目的 探讨影响结直肠癌预后的因素在预测结直肠癌术后生存中的价值。 方法 应用多因素回归的分析方法,回顾性分析有完整临床病理资料和随访资料的941例结直肠癌患者的临床特点、病理特征及其对预后的影响。 结果 结直肠癌患者总的3,5年生存率分别为63.2%和60.8%,中位生存时间为1841d。单因素分析显示,其预后与肿瘤的大体分型、侵袭程度、转移情况、分化等级、病理分期以及癌性肠梗阻均有相关性。应用Cox比例危险回归模型分析,则显示肿瘤的大体分型、分化程度、肠壁的侵袭深度和病理分期是影响结直肠癌患者术后生存的独立因素。 结论 病理分期是影响结直肠癌预后最重要的一个指标(P<0.0005),对于指导手术治疗、术后辅助治疗和判断预后方面具有重要作用。  相似文献   

20.
目的 分析艾滋病病毒(HIV)感染者/艾滋病(AIDS)合并恶性肿瘤患者的临床特点及生存预后情况。方法 回顾性分析354例艾滋病合并恶性肿瘤患者资料,采用Log-rank检验进行单因素分析,采用Cox比例风险回归模型进行多因素分析。结果 患者平均年龄54.10±12.96岁,男女比例2.1:1,艾滋病合并淋巴瘤的患者最多(28.25%);1、3、5年生存率分别为78.48%、62.13%、55.31%。单因素分析显示不同恶性肿瘤类型、年龄、性别、医保类型、确诊合并艾滋病后住院次数、平均住院天数、是否放疗、有无遵医嘱离院等患者的预后差异均有统计学意义;多因素分析显示性别、入院次数、平均住院天数、自费比例以及有无遵医嘱离院是影响患者生存预后的独立危险因素。结论 艾滋病容易合并淋巴瘤、肺癌、宫颈癌。患者在医院接受抗肿瘤疗程不足。  相似文献   

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