HSPA5基因3′非翻译区多态性与肝细胞癌预后的关系

目的调查70 kDa热休克蛋白5（HSPA5）基因3′非翻译区的变异与肝细胞癌预后的关系。方法从288例肝细胞癌患者外周血中提取DNA,采用TaqMan检测HSPA5基因的rs16927997、rs1140763和rs12009。Kaplan-Meier方法和Log-rank检验用于评价总生存率。结果 HSPA5单体型的分布与临床特性不相关。单变量分析显示等位基因、基因型、单体型和双体型不影响生存。多重比较结果显示临床特征与病人总的预后无关（P〉0.05）。结论中国人HSPA5基因3′非翻译区的变异对HCC的预后没有明显影响。     

HSPA5基因3'UTR 区多态性与肝细胞癌的相关性

目的 调查70kDa热休克蛋白5(HSPA5)基因3'非翻译区(UTR)的多态性与HCC发病风险之间的关系.方法 从576例肝细胞癌患者和539例在性别和年龄上匹配的健康对照者外周血中提取DNA,采用TaqMan检测HSPA5基因3'UTR区的rsl6927997、rsll40763和rsl2009.结果 连锁不平衡的分析确定了3种单倍型和6种双倍型.等位基因、基因型、单体型和双体型在肝癌患者和正常对照组之间的分布没有显著差异.结论 本研究表明,HSPA5基因3'UTR的多态性不是有效预测肝细胞癌风险的诊断标志物.     

HSPA5基因3′UTR区多态性与肝细胞癌的相关性

目的调查70kDa热休克蛋白5（HSPA5）基因3′非翻译区（UTR）的多态性与HCC发病风险之间的关系。方法从576例肝细胞癌患者和539例在性别和年龄上匹配的健康对照者外周血中提取DNA,采用TaqMan检测HSPA5基因3′UTR区的rs16927997、rs1140763和rs12009。结果连锁不平衡的分析确定了3种单倍型和6种双倍型。等位基因、基因型、单体型和双体型在肝癌患者和正常对照组之间的分布没有显著差异。结论本研究表明,HSPA5基因3＇UTR的多态性不是有效预测肝细胞癌风险的诊断标志物。     

Interleukin-18基因启动子区单核苷酸多态性与肝细胞癌遗传易感性关系的研究

目的探讨白细胞介素18(IL-18)基因启动子区-607C/A(rs1946518)和-137G/C(rs187238)单核苷酸多态性(SNP)与肝细胞癌(肝癌)遗传易感性的关系。方法应用序列特异性引物-聚合酶链反应(PCR-SSP)技术,检测228例肝癌患者和300例健康对照者IL-18基因启动子-607C/A(rs1946518)、-137G/C(rs187238)单核苷酸多态性位点基因型,分析肝癌患者和对照组基因型频率和等位基因频率分布。结果肝癌组SNP位点rs187238 G等位基因的频率明显高于对照组(OR=1.1891,95%CI=1.0106-1.5633,P=0.026)。携带rs187238 GG基因型的肝癌患者较多(OR=1.5168,95%CI=1.1490-1.8322,P=0.010)。分层分析发现,rs1946518位点上AA基因型与肝癌发病的关联在饮酒的肝癌患者中更加显著(P=0.024),而且rs187238位点上GC/CC基因型与肝癌发病的关联在出现肝癌复发的患者中更加显著(P=0.005)。结论 IL-18基因启动子区-137G/C(rs187238)GG基因型与肝癌遗传易感性有关联。而rs1946518位点AA基因型和rs187238位点GC/CC基因型分别与肝癌患者饮酒和肝癌复发有关联。     

Survivin在肝细胞癌中的表达特点及其与预后的关系

目的: 研究原发性肝细胞癌组织中Survivin的表达及其与肝癌细胞的生物学行为及预后的关系。 方法: 应用免疫组织化学染色对83例肝癌及相应癌旁组织中Survivin蛋白的表达情况进行检测，应用半定量RT-PCR技术对11例肝癌及相应癌旁组织中Survivin mRNA的表达情况进行检测，结合临床病理资料分析。 结果: 肝癌及癌旁组织中Survivin蛋白的表达率分别为63.9%(53例)和39.6%(21例)。肝癌组织中，41.5%(22例)表达于肝癌细胞核，45.3%(24例)表达于肝癌细胞浆，13.2%(7例)在胞核、胞浆中均有表达。统计学分析表明，Survivin蛋白阳性反应定位于胞核的病例，其肿瘤的包膜侵犯率和转移率更高 (P<0.05)；且术后生存期<2年的肝癌组中的核表达率显著高于术后生存期≥2年者(P<0.01)。RT-PCR结果显示，11例肝癌组织均表达Survivin mRNA，而癌旁组织只有45.5%(5例)表达。 结论: Survivin在肝癌中呈现高表达，其核表达与肝癌的恶性生物学行为及预后密切相关。     

肝细胞癌组织中HBx基因蛋白表达与凋亡关系

乙型肝炎病毒(hepatitis B virus，HBV)感染是肝细胞癌(hepatocellular carcinoma，HCC)发生的主要病因之一，HHx基因具有癌基因的特性，其表达产物HBx蛋白具有转录激活子功能，在HCC的发生发展中起着重要的作用。研究HBx蛋白的表达及其对细胞凋亡的调节有助于阐述HCC的发生发展机制。笔者利用S-P免疫组化方法和原位脱氧     

CEP55蛋白在原发性肝细胞癌组织中的表达与临床特征及预后的相关性分析

目的 分析中心体蛋白55(CEP55)在肝细胞癌(HCC)组织中的表达与临床特征及预后的相关性,为揭示肝癌诊断和治疗的新目标和策略提供依据.方法 基于TCGA-LIHC数据库分析CEP55在HCC和相应的正常组织中的表达差异,并进一步分析其与生存预后的关系.纳入185例于2015年4月至2016年7月在我院肝胆外科完成了肝切除术的HCC患者,对手术切除的肿瘤组织和癌旁组织(距离肿瘤边缘>5.0cm)制作组织蜡块.采用免疫组织化学染色法检测组织CEP55蛋白表达,分析CEP55表达与HCC患者不同临床特征的关系.采用Kaplan-Meier法绘制生存曲线,并使用Log-rank分析CEP55表达与预后的相关性.采用Logistic回归模型分析影响原发性肝癌患者预后的危险因素.结果 基于TCGA-LIHC数据库,418例肝癌组织中CEP55基因拷贝数明显高于癌旁正常组织(P<0.05),且根据每组CEP55表达水平的中位数值将患者分为两组.与LIHC队列中的低表达组相比,CEP55高表达组的总生存期(OS)和无进展生存期(PFS)明显缩短(Log-Rank检验,P<0.05).CEP55蛋白的表达与患者血管有无浸润、肿瘤直径、BCLC分期、T分期、N分期、分化程度、AFP水平有关(P<0.05).随访5年,CEP55蛋白高表达组和低表达组患者5年OS分别为64.9％(63/97)、84.0％(74/88)(Log-Rankχ2=10.192,P=0.001);5年PFS分别为54.6％(53/97)、69.3％(61/88)(Log-Rankχ2=5.750,P=0.016).经单因素和多因素Logistic回归分析,肿瘤组织CEP55高表达是影响患者预后的独立危险因素之一(P<0.05).结论 CEP55蛋白在HCC组织中普遍呈高表达,其与患者预后不良有关,可作为肝癌早期诊断或潜在治疗靶点的分子生物学指标.     

p53基因第72密码子多态性与中国人肝细胞癌遗传易感性的相关性

目的探讨在有无慢性乙型肝炎的不同背景下郦基因第72密码子多态性（R72P）与中国人肝细胞癌（hepatocellular carcinoma，HCC）遗传易感性的关系。方法采用聚合酶链反应-限制性片段长度多态方法，检测469例HCC（HBsAg阴性110例、HBsAg阳性359例）与567名对照（HBsAg阴性430例、HBsAg阳性137例）的郦R72P基因型分布及差异。结果全样本以及HBsAg阳性样本的HCC与对照问的基因型分布差异均无统计学意义。但在HBsAg阴性人群中，72P是HCC发生的危险因素（OR=1，69，95％CI=1，25～2．27）。与R／R基因型相比，R／P的HCC风险增加至1．73倍（95％CI=0．96～3．11），P／P的HCC风险显著增加至3．29倍（95％CI=1．58～6．86）。携带72P的男性个体、HCC家族史阳性个体的HCC风险分别进一步增加至9．39倍（95％CI=3，08～28．62）和11，14倍（95％CI=1，62～76．67）。结论皿形72P增加HBsAg阴性中国人的HCC风险，并与男性、HCC家族史在增加HCC风险中有协同作用。     

广西人群DNA修复基因XRCC3多态性与肝细胞癌遗传易感性关联分析

目的 探讨DNA修复基因X线修复交叉互补因子3(X-ray cross-complementing group 3,XRCC3)基因Thr241Met多态性与黄曲霉毒素B1(aflatoxin B1,AFB1)相关性肝细胞癌(hepatocellular carcinoma,HCC)遗传易感性的相关性.方法 应用PCR技术对AFB1高污染区广西地区257例HCC患者和711名对照人群的XRCC3基因多态性进行检测,进行的病例对照研究.结果 (1)XRCC3 3种基因型(Thr/Thr、Thr/Met、Met/Met)中带有Met者与HCC的易感性相关,且这种相关性与Met数量呈正相关(校正风险值OR分别为2.20和8.56);(2)XRCC3突变基因型多态与血白细胞AFB1-DNA加合物水平在HCC发生过程中存在协同作用(校正OR:2.34～20.44,P＜0.01).结论 XRCC3多态性与HCC易感性相关,且这种多态性与AFB1暴露水平在HCC发生中存在协同作用.     

CyclinA2基因多态性与肝细胞肝癌易感性的关系

目的 探讨CyclinA2启动子区单核苷酸多态性与肝细胞肝癌发病风险的关系。方法 选取2012年10月~2017年9月在九江市第一人民医院确诊的原发性肝细胞肝癌患者180例,同时选择行体检的健康志愿者180例作为对照组。分别采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对cyclinA2基因的rs769236位点进行多态性检测,比较不同基因型与原发性肝细胞癌发病风险的关系。结果 rs769236 等位基因A（GA+AA）携带者患原发性肝细胞癌的风险显著高于rs769236GG野生基因型的个体（校正OR=1.825,95%CI=1.133-2.940）。结论 CyclinA2基因rs769236（G/A）位点A变异可能会增加原发性肝细胞癌的发病风险。     

Novel polymorphisms in the promoter and 5' UTR regions of the human vascular endothelial growth factor gene

We have characterized 5 novel, single-nucleotide polymorphisms in the promoter and 5′ UTR regions of the human vascular endothelial growth factor (VEGF) gene. Transitions C → A at nucleotide position −2578 relative to the translation start site, T → C at position −1455, G → A at position −1154, G → C at position −1001, and C → T at position −7 were observed. In addition, individuals with the A allele at position −2578 also had an insertion of 18 nucleotides, whereas CC homozygotes did not contain this insertion. We have described the frequency distribution of the polymorphic alleles in the population of healthy volunteers and are investigating the functional significance of the 18-nucleotide insertion and of the single-nucleotide polymorphisms on VEGF gene expression.     

Novel PEX1 coding mutations and 5' UTR regulatory polymorphisms

Zellweger syndrome and its milder variants--neonatal adrenoleukodystrophy and infantile Refsum disease--comprise a clinical continuum of diseases referred to as the Zellweger spectrum. Mutations in the PEX1 gene, which consists of 24 exons and encodes a AAA ATPase protein required for peroxisomal protein import, account for approximately two-thirds of the known Zellweger spectrum patient mutations. In this paper, we report on four novel PEX1 mutations and two polymorphisms in an Australasian cohort. Two of the mutations--c.1108_1109insA and c.2391_2392delTC--that lead to the introduction of a premature termination codon in exons 5 and 14, respectively, are associated with the severe Zellweger phenotype. One patient with a milder disease phenotype was a compound heterozygote for two missense mutations (I989T and R998Q), both affecting amino acids in the second, C-terminal AAA domain of the protein. PTS1 protein import levels in cultured skin fibroblasts from this patient were almost 20% of normal control levels. We have also characterized two co-segregating polymorphisms in the 5' UTR of the PEX1 gene. Based on reporter assays, the c.-137T>C polymorphism leads to reduced PEX1 expression, whereas the c.-53C>G polymorphism leads to increased expression. When present together, these regulatory polymorphisms lead to near-normal PEX1 expression. Altered PEX1 expression due to the presence of either the c.-137T>C or the c.-53C>G variant could impact on residual PEX1 function if another co-allelic mutation was present which did not completely abolish PEX1 function. It also follows that the presence of polymorphisms in the PEX1 promoter region could have implications for patients with mutations in other PEX proteins known to interact with PEX1, such as PEX6. Thus, although not deleterious in control individuals, these polymorphisms could contribute to phenotypic heterogeneity among Zellweger spectrum patients.     

Association between ERCC5 gene polymorphisms and breast cancer risk

We conducted a case-control study to evaluate the association between ERCC5 polymorphism and breast cancer risk. 325 breast cancer patients and 325 controls were recruited in our study between January 2011 and March 2014. ERCC5 rs1047768, rs2094258, rs2296147, rs751402 and rs873601 polymorphisms were genotyped, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. By logistic regression analysis, we found that individuals with AA genotype of rs2094258 was associated with increased risk of breast cancer when compared with wide-type genotype, and the OR (95% CI) was 1.80 (1.12-2.92) for AA genotype. Individuals with GA + GG genotype of rs2094258 were significantly correlated with increased risk of breast cancer in tobacco smokers, and the OR (95% CI) was 7.35 (1.21-47.20). In conclusion, our study indicated that ERCC5 rs2094258 polymorphism may contribute to the risk of breast cancer.     

Association between polymorphisms in the SPINK5 gene and atopic dermatitis in the Japanese

Atopy, which is characterized by increased levels of immunoglobulin E (IgE) against common environmental allergens, is considered the strongest predisposing factor for asthma and atopic dermatitis (AD). Mutations in the gene encoding serine protease inhibitor Kazal-type 5 (SPINK5) are responsible for Netherton syndrome, a rare skin disorder characterized by greatly elevated IgE levels with atopic manifestations. A recent study of Caucasian AD families showed that maternally derived alleles of the SPINK5 gene are associated with development of AD and asthma, suggesting the parent-of-origin effect for the development of atopic diseases in the SPINK5 gene. We studied the possible association of the SPINK5 gene for the development of atopic diseases by determining the genotypes of five polymorphisms in a Japanese population. Ttransmission disequilibrium tests revealed an association of SPINK5 polymorphisms with AD but not with asthma. Our data indicate that the SPINK5 gene is associated with AD across ethnicities.     

B及T细胞弱化因子基因多态性与乳腺浸润性导管癌临床关系的研究

目的 探讨B及T淋巴细胞弱化因子(BTLA)基因多态性与妇女乳腺浸润性导管癌临床关系;确定BTLA基因多态性与妇女乳腺浸润性导管癌临床关系的相关性.方法 取280例患乳腺浸润性导管癌妇女的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行BTLA基因单核苷酸多态性检测,引用统计学软件分析其与各临床指标间的关系.结果 BTLA基因的rs1844089基因型与雌激素受体(ER)、孕激素受体(PR)和P53基因表达有关,rs2705535基因型与PR表达有关,rs9288952基因型与肿瘤大小,ER表达及PR表达有关.结论 BTLA的基因多态性中SNP的基因型与乳腺浸润性导管癌患者的肿瘤大小、ER、PR及P53基因差异具有统计学意义,而与淋巴结转移未发现有相关性.     

B及T细胞弱化因子基因多态性与乳腺浸润性导管癌临床关系的研究

目的 探讨B及T淋巴细胞弱化因子(BTLA)基因多态性与妇女乳腺浸润性导管癌临床关系;确定BTLA基因多态性与妇女乳腺浸润性导管癌临床关系的相关性.方法 取280例患乳腺浸润性导管癌妇女的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行BTLA基因单核苷酸多态性检测,引用统计学软件分析其与各临床指标间的关系.结果 BTLA基因的rs1844089基因型与雌激素受体(ER)、孕激素受体(PR)和P53基因表达有关,rs2705535基因型与PR表达有关,rs9288952基因型与肿瘤大小,ER表达及PR表达有关.结论 BTLA的基因多态性中SNP的基因型与乳腺浸润性导管癌患者的肿瘤大小、ER、PR及P53基因差异具有统计学意义,而与淋巴结转移未发现有相关性.     

B及T细胞弱化因子基因多态性与乳腺浸润性导管癌临床关系的研究

目的 探讨B及T淋巴细胞弱化因子(BTLA)基因多态性与妇女乳腺浸润性导管癌临床关系;确定BTLA基因多态性与妇女乳腺浸润性导管癌临床关系的相关性.方法 取280例患乳腺浸润性导管癌妇女的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行BTLA基因单核苷酸多态性检测,引用统计学软件分析其与各临床指标间的关系.结果 BTLA基因的rs1844089基因型与雌激素受体(ER)、孕激素受体(PR)和P53基因表达有关,rs2705535基因型与PR表达有关,rs9288952基因型与肿瘤大小,ER表达及PR表达有关.结论 BTLA的基因多态性中SNP的基因型与乳腺浸润性导管癌患者的肿瘤大小、ER、PR及P53基因差异具有统计学意义,而与淋巴结转移未发现有相关性.