长链非编码RNA TUG1在结肠直肠癌组织中的表达与分析

目的:检测结肠直肠癌组织长链非编码RNA牛磺酸上调基因1(taurine upregulated gene1,TUG1)的表达,并探讨其与结肠直肠癌临床病理因素及预后的相关性及临床意义。方法:采用实时定量聚合酶链反应检测106例结肠直肠癌病人的癌组织与相应的癌旁组织(距癌组织边缘5 cm)TUG1表达。分析TUG1表达与临床病理的相关性以及TUG1表达与结肠直肠癌预后的相关性。术后随访3~60个月。结果:TUG1在结肠直肠癌组织中表达明显高于癌旁组织(P=0.003),表达水平与肿瘤直径(P0.001)、CEA水平(P=0.049)以及TNM分期(P=0.005)密切相关。TUG1高表达的结肠直肠癌病人,生存率低于低表达病人(P=0.002 5)。多因素分析表明,TUG1可作为结肠直肠癌病人的独立预后因素。结论:TUG1在结肠直肠癌的发生发展中起重要作用,可作为反映结肠直肠癌生物学行为的有效指标。     

胰腺癌中Ring1B、LSD1及P16表达及其与预后的关系

目的:探讨胰腺癌中E3泛素连接酶亚单位Ring1B、组蛋白赖氨酸特异性去甲基化酶1(LSD1)及细胞周期调节因子P16表达与及其与患者预后的关系。方法:用免疫组化法检测85例胰腺癌患者手术标本(癌组织与癌旁组织)中LSD1、Ring1B与P16蛋白的表达及分布,并选取其中6对癌组织和癌旁组织,用qRT-PCR和Western blot法检测mRNA和蛋白表达;分析三者在胰腺癌组织中表达的相关性,及其与患者生存的关系。结果:免疫组化结果显示,Ring1B与LSD1蛋白主要表达于细胞浆,P16主要表达于胞核;Ring1B与LSD1在胰腺癌组织中表达明显高于癌旁组织,而P16的表达明显低于癌旁组织(均P0.05);在胰腺癌组织中Ring1B、LSD1的表达与P16的表达均呈负相关(r=-476;r=-0.673,均P0.05)。qRTPCR结果显示,胰腺癌组织中Ring1B和LSD1的mRNA的平均相对表达量均明显高于癌旁组织(8.908vs.1.947;7.126 vs.1.940,均P0.05),P16的mRNA的平均相对表达量明显低于癌旁组织(1.269vs.5.237,P0.05);Western blot结果显示,三者的蛋白表达趋势与mRNA表达一致。生存分析显示,Ring1B、LSD1高表达患者生存率均分别低于其低表达患者(χ~2=8.958,P=0.012;χ~2=8.856,P=0.010),而P16高表达患者生存率高于其低表达患者(χ~2=7.867,P=0.024)。结论:胰腺癌组织中Ring1B与LSD1表达升高,P16表达降低;Ring1B、LSD1可能分别通过组蛋白泛素化和去甲基化调控P16的表达,从而影响胰腺癌预后。     

结直肠癌组织中GLUT-1和VEGF-A的表达与临床病理特征及预后的关系

目的:检测葡萄糖转运蛋白-1(GLUT-1)和血管内皮生长因子A(VEGF-A)在结直肠癌组织中的表达,评价其与结直肠癌临床病理特征和预后的关系。方法:采用免疫组织化学法检测95例结直肠癌组织及癌旁正常组织中的GLUT-1和VEGF-A的表达,分析两者表达相关性及与临床病理特征和预后的关系。结果:GLUT-1和VEGF-A在癌组织中表达明显高于癌旁组织(P0.05);GLUT-1和VEGF-A的表达在有无淋巴结转移、不同TNM分期间差异有统计学意义(P0.05),在不同年龄、性别、肿瘤大小和分化程度间差异均无统计学意义(P0.05);Spearman相关性分析显示GLUT-1、VEGF-A两者在结直肠癌组化中的表达呈正相关(r=0.510,P0.05);Kaplan-Meier生存分析发现,GLUT-1和VEGF-A均为阳性表达患者的生存预后明显差于其他患者(χ~2=6.79,P=0.009);单因素分析显示肿瘤淋巴结转移情况、TNM分期和GLUT-1、VEGF-A表达是否均为阳性是影响患者生存的危险因素(P0.05),多因素分析显示,肿瘤淋巴结转移是影响患者生存的独立危险因素(P0.05)。结论:结直肠癌组织中GLUT-1和VEGF-A的表达高于正常组织,两者共同参与了结直肠癌的发生发展和转移过程,对患者的治疗和预后评估具有一定的参考价值。     

长链非编码RNA牛磺酸调节基因1和miR-132的表达与乳腺癌预后的关系

目的探讨乳腺癌中长链非编码RNA（LncRNA）牛磺酸调节基因（TUG）1和miR-132表达情况及两者表达水平与患者预后的关系。 方法收集2014年1月至2017年11月如皋市人民医院90例手术切除的乳腺癌组织和相应癌旁组织,采用qRT-PCR法检测TUG1和miR-132表达水平,使用Kaplan-Meier法计算TUG1和miR-132表达对乳腺癌患者生存率的影响,采用Cox回归模型分析乳腺癌预后的影响因素。 结果与癌旁组织相比,乳腺癌组织中TUG1表达水平明显升高（t=65.781,P<0.001）,miR-132表达水平显著下降（t=33.089,P<0.001）,均与雌激素受体（ER）、人表皮生长因子受体2（HER-2）、FIGO分期、分化程度和淋巴结转移相关（均P<0.05）。乳腺癌组织中TUG1和miR-132表达之间呈负相关关系（r=-0.767,P=0.025）。TUG1高表达者3年生存率为80.77%（42/52）,显著低于低表达者97.37%（37/38）（χ²=5.639,P=0.018）;miR-132低表达者3年生存率为81.25%（39/48）,显著低于高表达者95.24%（40/42）（χ²=4.085,P=0.043）。Cox回归分析发现,ER、HER-2、FIGO分期、分化程度、淋巴结转移、TUG1和miR-132均是乳腺癌患者预后的影响因素（均P<0.05）。 结论在乳腺癌组织中,TUG1表达水平显著上调,miR-132表达水平显著下调,且两者呈负相关,都是影响预后的独立因素。TUG1可能通过调控miR-132的表达发挥促癌基因的作用,有望成为乳腺癌独立预后标志物和治疗新靶点。     

胃癌组织YAP1、E-cadherin、N-cadherin表达及临床意义

目的:探讨YAP1、E-cadherin、N-cadherin在胃癌组织中表达及意义。方法:用免疫组化法检测胃癌组织芯片中135例患者癌组织和癌旁组织中YAP1、E-cadherin、N-cadherin表达,分析YAP1表达与E-cadherin、N-cadherin表达的关系,以及与胃癌患者临床病理因素以及预后的关系。结果:与癌旁组织比较,胃癌组织中YAP1表达明显升高,E-cadherin表达明显降低(均P0.05),N-cadherin表达无明显差异(P0.05);在胃癌组织中,YAP1表达与E-cadherin表达呈负相关(r=-0.273,P=0.032),与N-cadherin表达呈正相关(r=0.304,P=0.019)。YAP1在胃癌组织中的表达与胃癌患者淋巴转移、脉管侵犯有关(均P0.05),且YAP1阳性表达患者总生存率明显低于阴性表达患者(χ~2=4.354,P=0.037)。结论:YPA1与E-cadherin在胃癌组织中表达有明显变化,YAP1高表达与胃癌患者不良临床病理特征及预后密切相关。     

MACC1的表达与Klatskin瘤临床病理特征及预后的关系

目的 :探讨结肠癌转移相关基因1(MACC1)在Klats kin瘤中的表达情况及其与Klats kin瘤临床病理特征及预后的关系。方法:采用免疫组织化学染色,测定肿瘤组织和相应癌旁组织中MACC1蛋白的表达;采用实时荧光定量PCR方法,检测Klatskin肿瘤组织、癌旁组织和正常胆管组织中MACC1 mRNA的表达。分析MACC1的表达与临床病理特征及预后的关系。结果:肿瘤组织中MACC1蛋白的阳性表达率明显高于相应癌旁组织(P0.05);肿瘤组织中MACC1 mRNA的表达明显高于癌旁组织和正常胆管组织(P0.05)。Klatskin瘤组织中MACC1表达与肿瘤大小、复发、淋巴结转移有相关性(P0.05)。MACC1表达阳性和阴性患者1年、3年、5年的总生存率,差异有统计学意义(P0.05)。结论:MACC1在Klatskin瘤中呈现高表达,并与其肿瘤大小、复发、淋巴结转移有相关性,影响患者预后。     

转化生长因子β激活酶1在结肠癌中的表达及临床意义

目的:探讨转化生长因子β激活酶1(TAK1)在结肠癌组中的表达与临床意义。方法:收集141例结肠癌患者手术标本,用免疫组织化学方法检测TAK1蛋白在结肠癌及癌旁正常组织中的表达,并分析其表达与患者临床病理因素及预后的关系,同时检测结肠癌组织中K-ras基因突变情况,分析TAK1表达与K-ras基因突变的关系。结果:TAK1在结肠癌组织中的阳性表达率明显高于癌旁正常组织(68.8%vs.16.3%,P0.05);TAK1的阳性表达与Dukes分期、肿瘤分化程度和淋巴结转移有关(P0.05);TAK1阳性表达患者的5年生存率明显低于低表达的患者(P0.05);TAK1阳性表达的结肠癌组织K-ras基因的突变率明显高于TAK1阴性表达的结肠癌组织(52.6%vs.13.6%,P0.05)。结论:TAK1可能参与了结肠癌的恶性进展,且TAK1的表达可能与K-ras基因突变密切相关。     

JAK2/STAT3信号通路在肝细胞性肝癌中表达及意义

目的:探讨JAK2/STAT3信号通路在人肝细胞性肝癌(HCC)组织中的表达以及其意义。方法:用免疫组化法和Western blot法检测75例HCC组织及其相应的癌旁组织JAK2与STAT3蛋白的表达,分析两者与HCC患者病理特征及预后的关系。结果:JAK2与STAT3蛋白在HCC组织中的阳性表达率及表达量均高于相应的癌旁组织(62.7%vs.5.3%,69.3%vs.9.3%;均P0.05);JAK2与STAT3蛋白在HCC组织中的表达呈明显正相关(r=0.383,P0.01)。JAK2和STAT3蛋白的表达与肝硬化、门静脉癌栓、肿瘤分化程度、临床分期明显有关(均P0.05)。生存分析显示,JAK2与STAT3蛋白高表达患者的生存率及生存期均明显低于各自的低表达患者(χ2=13.591;χ2=6.842,均P0.05);Cox比例风险回归模型分析表明,JAK2与STAT3蛋白以及门静脉癌栓、肿瘤分化程度、临床分期均为影响HCC预后的独立危险因素(均P0.05)。结论:JAK2/STAT3信号通路在HCC组织中活性增高,且其活性高低与HCC患者预后密切相关。     

Snail在肝内胆管癌中的表达及其临床意义

目的:探讨Snail在肝内胆管癌组织中的表达及其与患者临床病理特征和生存预后的关系。方法:回顾性分析1999年12月—2010年1月外科手术治疗的55例肝内胆管癌病例及随访资料,免疫组织化学检测上述患者癌组织及癌旁组织标本中Snail的表达情况,分析Snail表达与临床病例资料、病理特征及预后的关系。结果:肿瘤组织中Snail表达量(2.764 vs.0.914)与高表达率(48.6%vs.18.0%)均明显高于癌旁组织(均P0.05),且Snail表达与肿瘤分化(χ~2=4.231,P=0.040)、TNM分期(χ~2=6.631,P=0.010)、淋巴结转移(χ~2=4.134,P=0.042)、微血管侵犯(χ~2=10.197,P=0.001)以及复发(χ~2=4.610,P=0.032)有关,与Snail低表达患者比较,Snail高表达患者总体生存率降低(P=0.018)、术后累计复发率升高(P=0.032)。单因素分析与多因素Cox回归模型分析结果示,微血管侵犯、淋巴结转移以及Snail表达是肝内胆管癌患者预后的独立影响因素(均P0.05)。结论:Snail在肝内胆管癌组织中表达增加,且Snail过表达与肝内胆管癌患者恶性病理特征及不良预后密切相关。     

PTEN蛋白与cyclin-D1蛋白在结肠癌中的表达及意义

目的 :研究人第10号染色体缺失的磷酸酶及张力蛋白同源的蛋白(PTEN蛋白)、细胞周期蛋白D1(cyclin-D1)在结肠癌中的表达及临床意义。方法:用免疫组化SP法检测78例结肠癌患者癌组织及癌旁正常黏膜组织中PTEN蛋白与cyclin-D1的表达情况,分析两者在结肠癌发生、发展过程中的表达情况及相互关系。结果:(1)PTEN蛋白在结肠癌组织中低表达,在正常黏膜组织高表达(P0.05),并随着肿瘤分化程度的降低、临床分期的提高、浸润深度的加深、淋巴结的转移而降低(P0.05)。(2)cyclin-D1在结肠癌组织中高表达,在正常黏膜组织低表达(P0.05),并随着肿瘤分化程度的降低、临床分期的提高、浸润深度的加深、淋巴结的转移而升高(P0.05)。(3)PTEN蛋白及cyclin-D1在肿瘤细胞中的表达呈负相关。结论:PTEN蛋白表达下调、cyclin-D1上调与结肠癌的发生、发展、浸润、转移有关,对两者的检测有助于对结肠癌患者做出病情评估及预测预后。     

CYP1A1与GSTM1基因多态性与前列腺癌易感性的关系

目的　探讨CYP1A1、GSTM1基因多态性与前列腺癌遗传易感性的关系。　方法　采用寡核苷酸芯片对 83例前列腺癌患者和 115例正常对照的中国汉族人群基因组DNA进行CYP1A1、GSTM1基因多态性分析。　结果　GSTM1基因缺失型前列腺癌组占 5 7.8% ,对照组 4 1.7% ,差异有显著性意义 ( χ2 =4 .99,P =0 .0 2 5 ) ,GSTM1null基因型使患前列腺癌的危险度增加 1.9倍 ( 95 %CI=1.10～ 1.34)。GSTM1基因缺失型前列腺癌患者的平均年龄 [( 6 8.1± 8.3)岁 ]低于GSTM1未缺失的患者[( 71.9± 7.4 )岁 ,P =0 .0 31]。前列腺癌组CYP1A1基因的两个多态位点m1、m2基因型频率和等位基因的频率与对照组相比差异无显著性意义 (P >0 .0 5 )。　结论　中国汉族人群GSTM1基因多态性与前列腺癌的发生相关 ,可能是增加前列腺癌危险和发病年龄早的因素之一。CYP1A1基因m1和m2的基因多态与中国汉族人群前列腺癌的发生无相关性     

COL1A1 haplotypes and hip fracture

Fragility fractures resulting from low‐trauma events such as a fall from standing height are associated with osteoporosis and are very common in older people, especially women. Three single nucleotide polymorphisms (SNPs) at the COL1A1 gene (rs1107946, rs11327935, and rs1800012) have been widely studied and previously associated with bone mineral density (BMD) and fracture. A rare haplotype (T‐delT‐T) of these three SNPs was found to be greatly overrepresented in fractured individuals compared with nonfractured controls, thus becoming a good candidate for predicting increased fracture risk. The aim of our study was to assess the association of this haplotype with fracture risk in Spanish individuals. We recruited two independent groups of ～100 patients with hip fracture (a total of 203 individuals) and compared the genotype and haplotype distributions of the three SNPs in the fractured patients with those of 397 control individuals from the BARCOS Spanish cohort. We found no association with risk of fracture at the genotype level for any of the SNPs, and no differences in the SNP frequencies between the two groups. At the haplotype level, we found no association between the T‐delT‐T haplotype and fracture. However, we observed a small but significant (p = 0.03) association with another rare haplotype, G‐insT‐T, which was slightly overrepresented in the patient group. © 2012 American Society for Bone and Mineral Research.     

Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer

BACKGROUND: Alcohol intake and tobacco smoke, in addition to other environmental and genetic factors, have been associated with head and neck cancer. We evaluated the role of metabolic enzyme polymorphisms on the risk of head and neck cancer in a hospital-based case-control study. METHODS: CYP1A1MspI, CYP2E1PstI, GSTM1, and GSTT1polymorphisms were evaluated in 103 histologically confirmed head and neck cancer cases and 102 controls by means of polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: GSTM1null increased the risk of head and neck cancer (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 1.24-3.79), oral cancer (OR, 2.8; 95% CI, 1.28-5.98), and pharyngeal cancer (OR, 2.2; 95% CI, 1.08-4.63). CYP2E1PstI polymorphism indicated a risk for oral cancer (OR, 3.6; 95% CI, 1.29-11.56). The joint effect of GSTM1 null and CYP1A1 polymorphism increased the risk of head and neck cancer (OR, 2.4; 95% CI, 1.13-5.10). CONCLUSIONS: GSTM1 null alone or associated with CYP1A1 increased the risk of head and neck cancer; the CYP2E1PstI mutated allele increased the risk for only oral cancer.     

Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status

EWSR1-CREB1 and EWSR1-ATF1 are gene fusions of which one or both have now been consistently described in 5 histopathologically and behaviorally diverse neoplasms: angiomatoid fibrous histiocytoma, conventional clear cell sarcoma (of tendons and aponeuroses), clear cell sarcoma-like tumor of the gastrointestinal tract, hyalinizing clear cell carcinoma of the salivary gland, and primary pulmonary myxoid sarcoma. Some of the tumors in this group have been described only recently, and others have been the subject of recent genetic insights contributing to their characterization. These neoplasms are all rare; yet, the increasing frequency with which EWSR1-CREB1 and EWSR1-ATF1 fusions are being described in separate entities is noteworthy. The additional molecular mechanisms by which tumors with such variable morphologic, immunohistochemical, and clinical phenotypes are generated are yet to be understood. We review the clinicopathologic and molecular features of this group of neoplasms unified by the presence of EWSR1-CREB1 and EWSR1-ATF1 genetic fusions.     

Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival

ObjectivePrognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer.Methods and materialsA total of 260 histologically confirmed patients were recruited from a voluntary screening, and genomic DNA was obtained from their blood samples for genotyping analyses to detect the CYP1A1*2A polymorphism and GSTM1 and GSTT1 deletions. The progression of illness and mortality were estimated with a median follow-up of 8.82 years. Adjusted estimated genotype risks were evaluated by hazard ratio and 95% CI using the Cox proportional model. In addition, the Kaplan-Meier survival method and log-rank test were used to evaluate patient survival with regard to genotype.ResultsThe 9-year overall and specific survival rates were 67.6% and 36.6% in the GSTT1null group, 67.6% and 58.7% in the GSTM1non-null group, 69.0% and 51.6% in the *1A/*2A group, 63.9% and 61.5% in the *2A/*2A group vs. 76.2% and 62.3% in the GSTT1non-null group, 82.3% and 50% in the GSTM1null group, and 83.7% and 56.3% in the *1A/*1A group, respectively. The hazard ratios and the Kaplan-Meier curve results demonstrate that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes are significantly associated with mortality. Our study has two main limitations: a relatively small sample size and a low global mortality percentage (25.4%); thus, we need to continue the follow-up to confirm these findings.ConclusionsOur results suggest that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes may be good prognosis markers, particularly in patients with high-risk tumors.     

DQA1 and DQB1 association and nasal polyposis.

OBJECTIVE: The aim of this study was to determine the contribution of the human major histocompatibility complex (HLA)-DQA1, -DQB1, and TNFalpha genes with simple nasal polyposis. STUDY DESIGN AND SETTING: A comparative case-control study with 31 patients and 151 controls was performed. HLA-DQA1, -DQB1, and TNFalpha -238 promoter position loci were typed by polymerase chain reaction (PCR) and sequence specific oligonucleotide probes (SSOPs). TNFalpha -308 promoter position was determined by PCR and digestion with NcoI restriction enzyme. RESULTS: The allele HLA-DQA1*0201 (P(c) = 0.019) had an etiologic fraction (EF) of 17%, whereas 13% EF was found for the haplotype HLA-DQA1*0201-DQB1*0201 (P = 0.016). Analysis of -DQB1 and TNFalpha promoter did not show significant differences between cases and controls. CONCLUSIONS: HLA-DQA1*0201-DQB1*0201 haplotype is involved in susceptibility, conferring 5.53 times more risk of developing this disease. EBM rating: B-2b.     

GSTT1, GSTM1, and CYP1B1 gene polymorphisms and susceptibility to sporadic renal cell cancer

PurposeTo estimate the prevalence and importance of GSTT1, GSTM1, and CYP1B1 genotypes in renal cell carcinoma (RCC), and to identify their value as a prognostic factor.Materials and methodsCross-sectional study of a group of patients diagnosed with RCC (n = 133) and a control group (n = 208) with benign conditions and no history of tumor. Controls were selected by cumulative samples and mixed pairing. All subjects pertained to the catchment area for our hospital. Sociodemographic variables, anatomical pathology features, and presence of GSTT1, GSTM1, and CYP1B1 polymorphisms by multiplex PCR and sequencing techniques.ResultsThere were no differences in the genotype distribution of the GSTT1 and GSTM1 genes between cases and controls. In the case of CYP1B1, the GG genotype (Ala119) was more prevalent in patients with RCC (OR = 2.08; 95% CI: 1.32–2.28) and may be implicated in 34.3% (95% CI: 16.3–52.2) of RCCs. In patients with GSTT1 deletion, TNM stages III to IV were more common (39.1%); whereas in Val432 homozygous patients in CYP1B1, Fuhrman grades 3 to 4 (54.6%) were more common. Because this was a cross-sectional study, longitudinal studies are needed in the future to confirm these data.ConclusionsNo relationship between GSTT1 and GSTM1 genotypes and RCC risk was observed. Homozygous subjects with Ala119 in CYP1B1 had twice the risk of RCC as homozygous for Ser119 or heterozygotes. Patients with GSTT1 deletion had tumors of more advanced stages, and those with Val432 polymorphism in CYP1B1 had tumors of higher Fuhrman grade.     

The HLA-DPB1--associated component of the IDDM1 and its relationship to the major loci HLA-DQB1, -DQA1, and -DRB1

The major histocompatibility complex (MHC) HLA region on chromosome 6p21 contains the major locus of type 1 diabetes (IDDM1). Common allelic variants at the class II HLA-DRB1, -DQA1, and -DQB1 loci account for the major part of IDDM1. Previous studies suggested that other MHC loci are likely to contribute to IDDM1, but determination of their relative contributions and identities is difficult because of strong linkage disequilibrium between MHC loci. One prime candidate is the polymorphic HLA-DPB1 locus, which (with the DPA1 locus) encodes the third class II antigen-presenting molecule. However, the results obtained in previous studies appear to be contradictory. Therefore, we have analyzed 408 white European families (200 from Sardinia and 208 from the U.K.) using a combination of association tests designed to directly compare the effect of DPB1 variation on the relative predisposition of DR-DQ haplotypes, taking into account linkage disequilibrium between DPB1 and the DRB1, DQA1, and DQB1 loci. In these populations, the overall contribution of DPB1 to IDDM1 is small. The main component of the DPB1 contribution to IDDM1 in these populations appears to be the protection associated with DPB1*0402 on DR4-negative haplotypes. We suggest that the HLA-DP molecule itself contributes to IDDM1.