MiR-429及Bmi-1 mRNA在弥漫性大B细胞淋巴瘤中的表达及其临床意义

目的：研究miR-429和Bmi-1 mRNA在弥漫性大B细胞淋巴瘤（DLBCL）组织中的表达及其临床意义。方法：选取自2014年1月—2015年12月河北医科大学第四医院的45例DLBCL患者瘤组织和28例正常对照人群淋巴结组织，用实时荧光定量反转录PCR（RT-qPCR）技术检测组织中miR-429及Bmi-1 mRNA的表达水平，并分析二者之间的关系及其与患者临床病理指标之间的关系。结果：DLBCL组织中miR-429表达水平较正常淋巴结组织明显降低，而Bmi-1 mRNA的表达水平明显升高（P < 0.01）。miR-429低表达组和Bmi-1 mRNA高表达组患者临床分期、骨髓浸润程度、Ki-67阳性率和IPI积分均分别高于miR-429高表达组和Bmi-1 mRNA低表达组（P < 0.05）。结论：DLBCL组织中miR-429及Bmi-1 mRNA的表达水平与患者病情进展和预后密切相关。组织中低表达miR-429及高表达Bmi-1 mRNA可能是患者临床预后较差的预测指标。     

MiR-429及Bmi-1 mRNA在弥漫性大B细胞淋巴瘤中的表达及其临床意义

目的:研究mi R-429和Bmi-1 m RNA在弥漫性大B细胞淋巴瘤(DLBCL)组织中的表达及其临床意义。方法:选取自2014年1月-2015年12月河北医科大学第四医院的45例DLBCL患者瘤组织和28例正常对照人群淋巴结组织,用实时荧光定量反转录PCR(RT-q PCR)技术检测组织中mi R-429及Bmi-1 mRNA的表达水平,并分析二者之间的关系及其与患者临床病理指标之间的关系。结果:DLBCL组织中mi R-429表达水平较正常淋巴结组织明显降低,而Bmi-1 mRNA的表达水平明显升高(P<0.01)。mi R-429低表达组和Bmi-1 mRNA高表达组患者临床分期、骨髓浸润程度、Ki-67阳性率和IPI积分均分别高于miR-429高表达组和Bmi-1 m RNA低表达组(P<0.05)。结论:DLBCL组织中mi R-429及Bmi-1 mRNA的表达水平与患者病情进展和预后密切相关。组织中低表达miR-429及高表达Bmi-1 mRNA可能是患者临床预后较差的预测指标。     

弥漫大B细胞淋巴瘤survivin和caspase-3表达的临床意义

目的探讨弥漫大B细胞淋巴瘤survivin、caspase-3表达与临床预后的关系。方法收集1997年至2000年间初治弥漫大B细胞淋巴瘤94例,用免疫组化SP法检测其survivin、caspase-3表达情况。应用SPSS10．0软件进行生存分析,并对各临床指标与预后的关系进行单因素和多因素分析。结果94例弥漫大B细胞淋巴瘤的survivin和caspase-3阳性表达率分别为68．1％和76．6％,其表达与国际预后指数（IPI）显著相关（P〈0．05）。survivin和caspase-3表达阳性患者的复发率高,survivin阳性患者的5年生存率（31．3％）明显低于survivin表达阴性患者（64．0％,P〈0．05）。多因素分析显示,survivin表达是弥漫大B细胞淋巴瘤的独立预后指标。结论survivin和caspase-3可作为弥漫大B细胞淋巴瘤的疗效和预后指标,与IPI结合可在早期筛选出常规治疗预后不良的病例,有助于指导临床治疗,改善预后。     

Clinical significance of nm23-H1 proteins expressed on cell surface in non-Hodgkin's lymphoma.

The nm23 gene was isolated as a metastasis suppressor gene that exhibits low expression in high-level metastatic cancer cells. Its gene is related to the prognosis of acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL). In this study, we examined the expression of nm23-H1 protein on the lymphoma cell surface of NHL. In 28 of 108 cases (25.9%), we observed > or = 20% of cell surface nm23-H1 protein expression and expression was especially high in peripheral T cell lymphomas and extranodal NK/T cell lymphomas. We also observed a significant correlation between serum nm23-H1 level and cell surface nm23-H1 expression levels. In patients with high levels of cell surface nm23-H1 expression, overall and progression-free survival rates were significantly lower than those in patients with low surface nm23-H1 expression levels. When surface nm23-H1 and serum nm23-H1 were combined, patients with high levels of both exhibited a poorer prognosis than patients with a high level of one or the other. These results indicate that in addition to serum nm23-H1, cell surface nm23-H1 may be used as a prognostic factor in planning a treatment strategy. The nm23-H1 protein appears to be intimately related to biological aggressiveness of lymphoma and, therefore, might be a molecular target of NHL treatment.     

PIM1表达与弥漫大B细胞淋巴瘤患者预后的关系

背景与目的:Pim1是一种原癌基因,具有抑制肿瘤细胞凋亡、促进肿瘤细胞增殖的功能.本研究旨在探讨PIM1蛋白与原发性弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)预后的关系.方法:采用免疫组化方法评估53例初治原发性DLBCL患者的PIM1表达,回顾性分析PIM1的表达与化疗反应性和总生存的关系.结果:PIM1蛋白高表达与DLBCL的负性预后相关,且它的表达与非生发中心的表型相关(r=0.404,P=0.003).PIM1蛋白高表达患者的3年总生存率和化疗完全缓解率均比低表达者低,差异有统计学意义(29.2%vs62.1%:29.2%vs 68.9%,P＜0.001和P=0.006).PIM1和国际预后指数(international prognostic index,IPI)的多因素分析表明,PIM1是总生存独立的预后因素(P=0.013).单因素Logistic回归分析表明,PIM1的表达与化疗的完全缓解率呈负相关.结论:在DLBCL患者中,PIM1的高表达可以作为一个临床预后不良标志.     

弥漫大B细胞淋巴瘤中B7-H1临床表达水平分析

目的 对弥漫大B细胞淋巴瘤(DLBCL)中B7-H1的表达水平进行分析.方法 收集DLBCL患者病理活检或手术切除的肿瘤组织标本50例,另收集瘤周正常淋巴组织标本50例作为对照.采用Western Blot法检测B7-H1在瘤周正常淋巴组织与DLBCL肿瘤组织中的表达水平;采用流式细胞仪检测瘤周正常淋巴组织与DLBCL肿瘤组织中B7-H1和调节性T细胞(Treg)的表达水平.结果 Western Blot检测结果显示,B7-H1在DLBCL肿瘤组织与瘤周正常淋巴组织中均有表达,与瘤周正常淋巴组织比较,DLBCL肿瘤组织中B7-H1的表达水平较高.HLA-DR+CD14+巨噬细胞在DLBCL肿瘤组织中表达B7-H1的比例较瘤周正常淋巴组织高(P﹤0.05).与瘤周正常淋巴组织相比较,DLBCL肿瘤组织中(包括IPI值≥2分与IPI值﹤2分)pDC、Treg、mDC与调节性T细胞(CD4+/CD8+)的比例较高(P﹤0.05).结论 B7-H1在DLBCL患者的淋巴组织中呈高表达,提示B7-H1与淋巴瘤细胞的免疫逃逸有关,从而造成了DLBCL细胞免疫平衡的失调.     

Clinical significance and prognosis of MYC translocation in diffuse large B-cell lymphoma

Recent studies have suggested that chromosomal aberrations of the MYC gene locus indicate an unfavorable prognosis in diffuse large B‐cell lymphoma (DLBCL). However, there have been few reports on MYC translocation in Chinese patients. One hundred and six cases of DLBCLs were analyzed using interphase fluorescent in situ hybridization. Immunophenotyping analysis (CD20, CD3, CD10, Bcl‐6, Mum‐1) was also performed. MYC translocation was identified in 13 (12.3%) out of 106 cases. All MYC⁺ DLBCLs showed a non‐germinal center B‐cell type. MYC⁺ DLBCLs showed significantly poorer overall survival (OS) and progression‐free survival, with a median OS and progression‐free survival time of 4.7 and 3.2 months, respectively (p < 0.001). Multivariate analysis using a Cox proportional hazard model confirmed that MYC⁺ (for OS, Hazards ratio 5.254; 95% CI, 2.354–11.723, p < 0.001) was the strongest independent predictor. DLBCL with MYC translocation is a subgroup of non‐germinal center B‐cell DLBCL with poor outcome. This may be a clinical characteristic that is specific to Chinese patients. Because only a few patients received rituximab, its usefulness could not be assessed. Future studies with larger numbers of patients are required. Copyright © 2011 John Wiley & Sons, Ltd.     

弥漫性大B细胞淋巴瘤患者血清中白细胞介素10表达的临床意义

目的探讨弥漫性大B细胞淋巴瘤(DLBCL)患者血清中白细胞介素10(IL-10)的表达及与临床特征、化疗疗效之间的关系。方法采用酶联免疫吸附试验(ELISA)分别测定62例新确诊的DLBCL患者(观察组)和62例健康者(对照组)血清中IL-10的表达。对两组IL-10的表达进行比较,对不同病理因素间IL-10的表达进行比较,2个周期化疗后对患者IL-10的表达与疗效进行相关分析。结果观察组患者血清中IL-10的表达明显高于对照组;观察组患者IL-10的表达与年龄、分期、美国东部肿瘤协作组(ECOG)评分、国际预后指数(IPI)评分、乳酸脱氢酶(LDH)、B症状、病理免疫分型、白蛋白密切相关,与性别、结外是否超过1处侵犯、血红蛋白无关;IL-10在化疗有效后的表达降低,化疗无效时的表达前后无明显变化,化疗前IL-10的表达较低者化疗有效率更高。结论DLBCL患者血清中IL-10的表达可间接反映DLBCL的生物学特征,可以作为观察DLBCL病情变化及预后的重要辅助指标。     

膀胱癌中MMP-2与nm23的表达及其临床意义

目的　探讨膀胱癌组织中的MMP - 2与nm2 3-H1蛋白的表达及其临床意义。方法　采用免疫组化S -P法分析 6 3例手术切除膀胱癌中MMP - 2与nm2 3-H1蛋白的表达情况。结果　MMP - 2在膀胱移行细胞癌与乳头状瘤中的表达有显著性差异 (P <0 0 5 ) ,其表达与肿瘤分级与临床分期呈正相关 ;nm2 3-H1蛋白表达与肿瘤分期呈负相关 ,在肿瘤组织中随TCCB临床病理分期升高 ,MMP - 2表达增高趋势有显著性差异 ,而nm2 3-H1的表达随TCCB分级及临床分期的升高而呈现降低趋势 ,且有显著性差异 (P <0 0 5 )。结论　检测膀胱癌转移相关基因表达并分析其表达的相互关系 ,有助于判断膀胱癌的转移潜能及指导术后干预治疗     

Mda-7/IL-24和C-myb在弥漫大B细胞淋巴瘤中的表达及其临床意义

目的：研究弥漫大B细胞淋巴瘤（DLBCL）中Mda-7/IL-24和C-myb的表达水平及其临床意义。方法：收集72例DLBCL患者的瘤组织及36例正常淋巴结组织;通过半定量逆转录PCR及免疫组化技术分别从mRNA及蛋白水平检测各组织中Mda-7/IL-24与C-myb的表达水平,并对Mda-7/IL-24与C-myb进行相关性分析;收集患者临床资料,分析瘤组织Mda-7/IL-24与C-myb蛋白表达水平与患者年龄、性别、临床分期、是否骨髓浸润、Ecog评分及国际预后指数（IPI）之间的关系;分析瘤组织Mda-7/IL-24与C-myb蛋白表达水平与患者无进展生存期之间的关系。结果：与正常淋巴结组织相比,DLBCL组织中Mda-7/IL-24 mRNA的表达水平明显降低,而C-myb mRNA的表达水平则明显增高（P < 0.01）;72例DLBCL患者瘤组织中Mda-7/IL-24与C-myb mRNA表达水平呈明显负相关（r=-0.43,P < 0.01）;瘤组织低表达Mda-7/IL-24、高表达C-myb的患者其临床分期晚、易骨髓转移、瘤细胞增殖活性强、IPI积分较高,同时患者无进展生存期较短（P均 < 0.05）。结论：DLBCL组织中Mda-7/IL-24与C-myb的表达呈明显负相关,Mda-7/IL-24低表达或C-myb高表达是DLBCL患者临床预后较差的指标。     

叉头框转录蛋白1在弥漫性大B细胞淋巴瘤中的表达及预后意义

目的 探讨叉头框转录蛋白1（FOXP1）在弥漫性大B细胞淋巴瘤（DLBCL）中的表达及其与DLBCL临床病理特征和预后的关系。方法 用免疫组织化学En Vision法检测85例DLBCL组织中FOXP1蛋白的表达情况,并分析FOXP1与临床病理特征及预后的关系。结果 85例DLBCL组织中FOXP1的阳性表达率为71.8％（61／85）,FOXP1表达与年龄、PS评分、乳酸脱氢酶（LDH）水平、国际预后指数评分、病理类型密切相关（P＜0.05）。在生发中心型（GCB）DLBCL中FOXP1阳性和阴性表达者的无病生存期（PFS）为13个月和44个月（P=0.002）,总生存期（OS）为28个月和50个月（P=0.003）;而在非生发中心型（non-GCB）中FOXP1表达与生存预后无关（P＞0.05）。单因素分析显示分期、LDH水平、有无B症状以及FOXP1表达与DLBCL患者的PFS和OS均相关（P＜0.05）,Cox多因素回归分析显示分期（95%CI：1.410~4.415,P=0.02）和FOXP1表达（95%CI：0.143～0.734,P=0.007）是PFS的独立预测因素。 结论 FOXP1蛋白有可能是DLBCL的一个重要的预后指标,尤其在GCB型DLBCL中FOXP1蛋白阳性表达提示预后不佳。     

Gene expression profiling of diffuse large B-cell lymphoma

Initial gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL) revealed that this single diagnosis actually encompasses two distinct diseases that differ in the expression of hundreds of genes. One subtype, germinal center B-cell-like (GCB) DLBCL, strongly resembles normal germinal center B-cells and has a good prognosis following chemotherapy, whereas activated B-cell-like (ABC) DLBCL resembles mitogenically activated blood B cells and has a poor outcome. An expanded analysis of 274 DLBCL cases confirmed the existence of the GCB and ABC subgroups, but demonstrated that additional subgroups exist. Furthermore, two recurrent oncogenic events in DLBCL, t(14;18) and amplification of the c-rel locus on chromosome 2p, were only observed in GCB DLBCL, whereas constitutive activation of NF-kappaB was seen in ABC DLBCL, showing that the gene expression subgroups represent pathogenetically distinct diseases. Gene expression profiling has also been used to identify individual genes that predict overall survival in DLBCL, the majority coming from gene expression signatures that reflect the cell of origin, proliferation rate, and host immune response to the tumor. A multivariate model including 17 genes representing these biological features divided patients with DLBCL into quartiles with strikingly distinct 5-year survival rates, ranging from 73% to 15%. The use of gene expression profiling should eventually lead to an integration of molecular diagnosis and consequent selection of the most appropriate treatment.     

Prognostic significance of nm23-H1 expression in oral squamous cell carcinoma

Recent studies indicated nm23-H1 played a role in cancer progression. Therefore, we investigated clinical significance of nm23-H1 expression in oral squamous cell carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23-H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and clinicopathologic variables were evaluated by chi(2) analysis. As increased size of primary tumour could escalate metastatic potential and the data of patients at the late T stage might confound statistical analyses, we thus paid special attention to 54 patients at the early T stage of OSCC. Statistical difference of survival was compared by a log-rank test. Immunohistochemically, nm23-H1 expression was detected in 48.8% (42 out of 86) of tumorous specimens. It positively correlated with larger primary tumour size (P=0.03) and inversely with cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased nm23 expression was associated with increased incidence of lymph node metastasis (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a prognostic factor for predicting better survival in OSCC patients at the early T stage, which may reflect antimetastatic potential of nm23. Therefore, modulation of nm23-H1 expression in cancer cells can provide a novel possibility of improving therapeutic strategy at this stage. In addition, our results further indicated cigarette smoking could aggravate the extent of nm23-H1 expression and possibly disease progression of OSCC patients.     

Biomarkers of potential prognostic significance in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous disease for which the current approach to treatment is only successful for 50% of patients. The prognostic value of various clinical and biological factors in predicting treatment outcome is discussed in this paper. A review of the English literature was performed including original articles and relevant reviews from MEDLINE that addressed the topics of DLBCL biology and potential prognostic factors. The International Prognostic Index is, to date, the most successful clinical model for predicting outcome. In addition, a rapidly expanding list of molecules has been identified by conventional and newer diagnostic methods that may be of significant prognostic value. Gene expression profiling has led to the discovery of new biological subtypes of DLBCL based on patterns of gene expression, and a host of new genes that may play important roles in this disease. Various derangements in apoptosis, cell-cycle regulation, differentiation, and signal transduction have been noted, while the host environment and immune response also appear to modify clinical outcome. Although to our knowledge, the fundamental abnormalities underlying DLBCL remain elusive, progress is being continuously made to further the understanding of the biological heterogeneity of this disease and the use of various clinical and biological variables to predict treatment outcome. The goal is to be able to identify subgroups of patients at high risk of treatment failure and develop more effective treatment based on specific biological defects that may represent new rational therapeutic targets.     

nm23-H1和MUC-1在外周T细胞淋巴瘤中的表达及其临床意义

背景与目的:外周T细胞淋巴瘤(peripheralT-celllymphoma,PTCL)是一类异质性疾病,临床侵袭性较强,常规治疗效果欠佳。国际预后指数(internationalprognosticindex,IPI)在PTCL中的价值尚未确定,有必要寻找一些分子指标来协助预测PTCL的预后。本研究旨在探讨nm23-H1和MUC-1对PTCL预后判断的价值。方法:免疫组化SP法检测中山大学肿瘤防治中心1997年1月至2004年12月间收治的96例初治PTCL患者组织中nm23-H1和MUC-1的表达情况,分析其表达与患者临床特征、近期疗效及远期生存率的关系。结果:96例患者nm23-H1和MUC-1的阳性率分别为81.2%(78/96)和58.3%(56/96);两者表达强度均与病理亚型无明显相关(P>0.05)。nm23-H1高表达与Ⅲ/Ⅳ期、PS状态≥2分、结外侵犯和结外病变数≥2等有关(P﹤0.05);而MUC-1高表达仅与分期Ⅲ/Ⅳ期、结外病变数≥2有关(P<0.05)。89例患者可评价化疗的客观疗效,全组有效率87.8%,完全缓解(CR)率56.7%。nm23-H1阴性者CR率高于阳性者(66.7%vs.55.4%,P<0.05),低表达组CR率高于高表达组(79.9%vs.44.0%,P<0.05);MUC-1阴性和低表达组的CR率分别高于阳性和高表达组,但均无显著性差异(P>0.05)。全组中位随访时间30个月(2～98个月),中位生存期32个月(95%CI26～34个月);nm23-H1阴性组5年生存率(overallsurvival,OS)明显高于阳性组(86.7%vs.24.9%,P=0.001),低表达组5年OS明显高于高表达组(52.3%vs.21.7%,P=0.000);MUC-1阴性组5年OS稍高于阳性组(47.9%vs.28.5%,P=0.260),低表达组5年OS稍高于高表达组(46.2%vs.22.2%,P=0.337)。多因素分析结果显示,IPI评分和nm23-H1表达水平是PTCL独立的预后指标。结论:nm23-H1在PTCL中过度表达提示预后不良,可作为判断PTCL预后的独立指标;MUC-1在PTCL中阳性及高表达与预后不良具一定的相关性,但对预后判断的价值尚不能确定。nm23-H1结合IPI评分等临床指标可能有助于更精确判断PTCL的预后。     

Clinical significance of 8q24/c-MYC translocation in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) has heterogeneous clinical, histological, and molecular features. We evaluated the clinical characteristics and prognoses of patients with DLBCL carrying 8q24 translocations. A total of 1864 consecutive patients with non-Hodgkin's lymphoma were treated in the Adult Lymphoma Treatment Study Group from 1998 to 2005. Of the 252 patients with DLBCL with abnormal karyotypes, 28 patients with DLBCL with the 8q24 translocation were identified. There were 14 men and 14 women, with a median age of 61 years. The 8q24 translocation was observed significantly more frequently among patients with poor performance status, among patients with high lactate dehydrogenase level, and among patients with bone marrow involvement. The 5-year overall survival was 43.9% among the patients with 8q24 translocation, and 67% among the patients with other chromosomal abnormalities. The 8q24 translocation group showed significantly poorer prognosis than the group with other translocations. In addition, patients with t(14;18) and 8q24 translocation showed significantly poorer prognosis than those with 8q24 translocation alone. It will be necessary to study whether more aggressive chemotherapy or rituximab combination chemotherapy is effective in 8q24 translocation cases. ( Cancer Sci 2009; 100: 233–237)     

MTAP、CDKN2A和CDKN2B在弥漫大B细胞淋巴瘤中的表达及其临床意义

 目的　研究弥漫大B细胞淋巴瘤（DLBCL）MTAP、CDKN2A和CDKN2B基因的表达及其临床意义。方法　以实时定量聚合酶链反应（PCR）方法检测40例DLBCL及19例淋巴结反应性增生组织中MTAP、CDKN2A和CDKN2B基因的表达情况,结合临床特征进行分析,并进行随访。结果　DLBCL组MTAP、CDKN2A和CDKN2B基因表达水平较淋巴结反应性增生组降低,差异有统计学意义（P值分别为0.024、0.044和0.047）;三者表达均与Ann Arbor临床分期相关（P值分别为0.004、0.001和0.027）;与患者的性别、年龄、淋巴结外病变累及、ECOG体力评分、骨髓累及、血清乳酸脱氢酶水平均无明显相关（均P＞0.05）。其中MTAP与CDKN2A基因表达情况还与B症状（P值分别为0.003和0.028）和国际预后指数（IPI）相关（P值分别为0.001和0.011）。此外,生存分析结果显示,MTAP、CDKN2A和CDKN2B基因表达水平与患者总生存期相关（P值分别为0.022、0.019和0.042）。结论　MTAP、CDKN2A和CDKN2B基因在DLBCL中呈低水平表达,与疾病进展和患者预后有关,可作为反映其生物学行为和评估患者临床疗效的分子标志物。     

Expression of nm23-H1 and nm23-H2 protein in endometrial carcinoma.

nm23 gene expression has been shown to be inversely correlated with tumour metastatic potential in some cancers but not in others. Examination was made of the expression of nm23-H1 and nm23-H2 gene products by immunohistochemistry and immunoblotting in 28 endometrial carcinomas. Immunohistochemistry indicated the cytoplasm of cancer cells to be positive, and myometrium and endometrial stromal cells negative, for nm23-H1 and -H2 protein. The staining intensity for these proteins was significantly stronger in well-differentiated adenocarcinomas (G1) than in those moderately differentiated (G2) (P < 0.05). nm23-H1 and -H2 proteins were shown by immunoblotting to be present at significantly higher levels in G1 than in G2 tumours (P < 0.05). Two of eight cases expressed high nm23-H1 and -H2 protein in poorly differentiated adenocarcinomas (G3). In G3 tumours, nm23 expression may be diverse. In this study, the expression of nm23-H1 and -H2 was not correlated with stage, metastasis, tumour size, myometrial invasion, oestrogen receptor, progesterone receptor or menopause. It follows from the findings presented above that the high expression of nm23-H1 and -H2 is positively correlated with histological differentiation.