肝癌组织中KLF17的表达及临床意义

目的 检测KLF17在肝癌组织的表达并评价其对肝癌预后的影响.方法 免疫组化法检测KLF17在肿瘤组织中的表达,以及KLF17表达对患者无进展生存和总生存期的影响.比较原代培养的Hep11和Hep12细胞侵袭和迁移的差异,以及KLF表达的差异.干扰KLF17表达后Transwell法检测Hep11迁移和侵袭的能力.结果 36名有随访结果并可评估的患者中,KLF17 0 ～2分19人,3～5分的17人.KLF17 3～5分的患者无进展生存期较0～2分的患者长,有统计学差异,分别为(39.3±4.2)个月和(23.4±4.9)个月(P＜0.05).KLF17 3～5分的患者总生存为(46.9±3.2)个月,KLF17 0 ～2分的患者为(35.2±4.2)个月(P＜0.05).在原代培养肝癌细胞中,来自原发灶的Hep11比来自转移复发灶的Hep12的KLF17表达高,Hep11的KLF17干扰后,迁移和侵袭能力增强(P＜0.05).结论 KLF17表达可能是肝癌患者预后的独立预测因素.     

SLC4A10表达水平对肝癌患者预后的影响

目的 通过生物信息学(生信学)分析在肝细胞癌(HCC)中SLC4A10的表达对HCC患者预后的影响,初步验证并探讨其意义.方法 通过TCGA数据库,分析SLC4A10在HCC组织与正常组织间的差异表达,并利用实时定量PCR进行验证.运用Kaplan-Meier(K-M)曲线分析SLC4A10的表达量对HCC患者预后的影...     

肝癌相关肿瘤标志物研究新进展

肝细胞癌( hepatocellular carcinoma, HCC )是常见的恶性肿瘤之一,其发病隐匿,恶性程度高,病死率高,因此早期诊断对于提高患者的生存率至关重要.目前临床上主要运用甲胎蛋白(alpha-fetoprotein, AFP )结合影像学及病理学检查进行肝癌的早期诊断;但是AFP对于肝癌筛查的特异性...     

肝细胞性肝癌中MAZ基因的表达及意义

目的探讨MAZ基因在肝细胞性肝癌(hepatocellular carcinoma,HCC)及其癌旁正常组织中的表达,分析其与HCC各临床病理特征及预后的关系。方法采用组织芯片技术和免疫组化法检测75例HCC及其对应癌旁正常组织中MAZ基因的表达,分析其与HCC临床病理特征及与患者预后的关系。结果 MAZ在HCC中的表达(48%,36/75)明显高于其癌旁正常组织(22.67%,17/75),组间比较差异有统计学意义(P0.05)。MAZ表达与HCC患者性别、年龄、病理分级、临床分期、TNM分期、是否合并肝硬化、是否合并乙肝病毒感染、是否有肝癌家族史以及血清AFP、CEA、γ-GT、ALT、AST和ALB水平、是否有淋巴结转移等均无明显相关性,而与肿瘤直径、吸烟与否、饮酒与否显著相关(P0.05)。HCC中MAZ阳性组和阴性组的累计生存率差异有显著性(P0.05),MAZ阳性组患者的术后无瘤生存时间明显低于阴性组,提示MAZ表达上调可能导致患者的预后更差。结论 MAZ基因表达上调可能与HCC的发生、发展密切相关。     

肝癌新的血清标志物：可能改善肝癌早期诊断的现状

原发性肝癌是目前世界上致死率最高的恶性肿瘤之一,在全世界范围内的发病率有逐年上升的趋势。早期诊断对肝癌患者的预后至关重要。对于肝癌的高危人群,现在最常用的监测手段是定期检测血浆中甲胎蛋白(AFP)水平和影像学检查如超声等。然而,甲胎蛋白的敏感性和特异性都不令人满意。近年来,蛋白组学技术的发展使得筛选新的肿瘤标志物成为可能,各种有希望的新的肿瘤标志物被相继发现,其中高尔基体蛋白73(GP73)最有可能成为更好的诊断肝癌,尤其是早期肝癌的血清标志物。在仅有的少数报道中,其敏感性可达69%,特异性可达90%,而其异构体敏感性和特异性可达90%和100%。除此之外,新发现的肝癌患者血清中高表达的标志物有甲胎蛋白异质体(AFP-L3)、异常凝血酶原(DCP)、α-L-岩藻糖苷酶(AFU)、磷脂酰基醇蛋白聚糖-3(GPC-3)、肝细胞生长因子(HGF)、转化生长因子β1(TGFβ1)、血管内皮生长因子(VEGF)、粘液素1(MUC-1,KL-1)等。这些新的血清标志物,正在被各种临床研究进行检测,有希望改变肝癌早期诊断和治疗的现状。我们正在进行GP73的大样本临床研究,取得初步结果。     

血管内皮生长因子在原发性肝癌组织中的表达及临床意义

目的:探讨血管内皮生长因子(VEGF)在原发性肝癌组织中的表达及其与肿癌的浸润转移的关系。方法:采用SP免疫组化法,检测60例原发性肝癌标本、30例癌旁组织和30例正常组织中VEGF的表达。结果:肝癌组的VEGF阳性表达率为68.3%,显著高于癌旁组(40.0%)和正常对照组(33.3%),有统计学差异(P<0.05);包膜不完整组织中VEGF阳性表达为92.9%,显著高于包膜完整组织(P<0.05);远处转移组织中VEGF阳性表达率为96.6%,显著高于无转移组织(P<0.05);而VEGF阳性表达在不同的TNM分期之间、肿瘤分化程度之间以及不同的病灶大小之间差异无统计学意义(P>0.05)。结论:VEGF在原发性肝癌组织中呈高表达,VEGF表达与肿瘤包膜有无和是否发生远处转移有关,VEGF在肝癌血管生成、生长及转移中起重要作用。     

CircRNAs in hepatocellular carcinoma: characteristic,functions and clinical significance

Hepatocellular carcinoma (HCC) is one of the most common and serious types of cancer worldwide, with high incidence and mortality rates. Circular RNAs (circRNAs) are a novel class of non-coding RNA with important biological functions. In recent years, multiple circRNAs have been found to be involved in the biological processes of tumorigenesis and tumor development. Increasing evidence has shown that circRNAs also play a crucial role in the occurrence and development of HCC. However, the specific molecular mechanism of circRNAs in HCC has not been fully elucidated. The present review systematically summarized the classification and basic characteristics of circRNAs, their biological functions and their role in the occurrence and development of HCC. By summarizing the previous studies on circRNAs in HCC, this study aimed to indicate potential approaches to improving the early diagnosis and treatment of HCC.     

Histological study of PIVKA-II expression in hepatocellular carcinoma and adenomatous hyperplasia

Although serum concentration of protein induced vitamin K absence or antagonist II (PIVKA-II) has been widely used for diagnosing hepatocellular carcinoma (HCC), little information is available concerning tissue PIVKA-II as an immunohistochemical marker for liver histology. In this study, we examined the expression of PIVKA-II in precancerous nodules (adenomatous hyperplasia) and various differentiation grades of HCC by immunohistochemical study using the monoclonal anti-PIVKA-II antibody (MU-3). We examined the relationship between tissue PIVKA-II staining and serum PIVKA-II level, tumor histology and tumor size. PIVKA-II was mainly detected in the cytoplasm of the HCC cells. The positive rates of PIVKA-II were as follows: adenomatous hyperplasia (AH), 0% (0/9); well-differentiated HCC, 65% (15/23); moderately differentiated HCC, 85% (22/26); poorly differentiated HCC, 54% (7/13). The expression of tissue PIVKA-II staining in moderately differentiated HCC was significantly higher than in well- or poorly differentiated HCC, whereas the serum PIVKA-II level in poorly differentiated HCC was higher than well- or moderately differentiated HCC. There was no relationship between the expression of PIVKA-II in cancer tissues and serum levels of PIVKA-II. Immunohistochemical studies revealed that PIVKA-II was expressed even in small-sized or well-differentiated HCC cells, but expression was not detected in AH. It was concluded that PIVKA-II is a useful immunohistochemical marker, even in small-sized or well-differentiated HCC.     

microRNA与肝癌

肝癌是世界上最常见的恶性肿瘤之一,其发病率和病死率极高。microRNA(miRNA)是一类单链的非编码RNA,通常在转录后水平调控基因的表达。最近多项研究表明miRNA在肝癌中发挥着重要作用,已经成为肝癌诊断、治疗中的一个靶标。     

SCNM1在乙肝相关性肝癌中的表达及临床意义

目的:研究钠离子通道调节蛋白1(SCNM1)在乙肝相关性肝癌中的表达情况,并探讨其表达差异与临床病理特征及预后的关系。方法:标本来源于2013年1月～2015年12月在中山大学附属第三医院接收治疗的108例乙肝相关性肝癌患者,所有患者均签署知情同意书,符合医学伦理学规定。结合公共数据库中的肝癌资料,分析SCNM1的m RNA表达水平;应用RT-qPCR检测乙肝相关性肝癌组织及癌旁组织中SCNM1的m RNA表达水平,并分析SCNM1的表达水平与乙肝相关性肝癌临床病理特征的关系;利用Kaplan-Meier plotter分析SCNM1与肝癌患者预后的相关性。结果:TCGA数据库、Human Protein Atlas数据库和Oncomine数据库的分析结果显示,SCNM1在肝癌组织中的表达量明显高于正常肝组织(P 0. 01)。SCNM1主要分布于细胞核中。RT-qPCR检测结果显示,乙肝相关性肝癌组织中SCNM1的m RNA中位表达水平明显高于其配对癌旁组织(t=8. 082,P 0. 01)。乙肝相关性肝癌患者中SCNM1的表达水平与肝硬化、丙氨酸转氨酶和肿瘤大小具有相关性(P 0. 05),而与患者的性别、年龄和肿瘤包膜等临床病理特征无相关,SCNM1高表达的肝癌患者总生存时间较低表的患者达短(HR=1. 53,P=0. 016),SCNM1高表达的乙肝相关性肝癌患者总生存时间更短(HR=2. 41,P=0. 015)。结论:在乙肝相关性肝癌中,SCNM1高表达并且和患者的预后相关。SCNM1在乙肝相关性肝癌的发生中可能起着重要作用。     

Real-time PCR检测脊髓钝挫伤大鼠TPM4基因的变化

目的观测TPM4在大鼠脊髓钝挫伤后的基因变化,探讨其在脊髓损伤修复中的作用。方法 SD成年大鼠20只,分为假手术组,脊髓钝挫伤12h组,脊髓钝挫伤3d组,脊髓钝挫伤7d组。取损伤段脊髓,通过Q-PCR检测TPM4的基因含量。结果 Q-PCR结果显示大鼠脊髓钝挫伤后12h,脊髓中的TPM4基因表达开始降低,于损伤后3d达最低,损伤后7d逐渐开始增加,均有统计学意义(P0.05)。结论大鼠脊髓损伤后,脊髓中TPM4基因含量变化先降低再升高,提示TPM4可能参与脊髓钝挫伤后的修复。     

Prognostic significance of long non-coding RNA PCAT-1 expression in human hepatocellular carcinoma

Background: Long non-coding RNAs (lncRNAs) play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in hepatocellular carcinoma (HCC) are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA PCAT-1 expression in HCC and evaluate its clinical significance in the development and progression of HCC. Methods: We examined the expression of PCAT-1 in 117 HCC tissues and adjacent non-tumor tissues using quantitative real-time-PCR and analyzed its correlation with the clinical parameters. Results: Our data showed that PCAT-1 expression in HCC tissues was significantly increased compared with adjacent non-tumor tissues (P<0.05). Up-regulated expression of PCAT-1 was significantly associated with TNM stage and metastasis (P<0.05), but not other clinical parameters. Moreover, Kaplan-Meier survival analysis showed that a high expression level of PCAT-1 resulted in a significantly poor overall survival of HCC patients. The multivariate Cox regression analysis demonstrated that PCAT-1 expression level was an independent prognostic factor for the overall survival rate of HCC patients. Conclusions: Our data suggested that the increased expression of PCAT-1 was associated with advanced clinical parameters and poor overall survival of HCC patients, indicating that PCAT-1 up-regulation may serve as a novel biomarker of poor prognosis in HCC patients.     

URG4在肝癌组织中的表达及其与HBx的关系

目的:检测URG4在肝癌组织中的表达及意义。探讨URG4与HBx在肝癌组织表达之间的关系。方法:免疫组化方法检测URG4和HBx在正常组织、肝癌组织及癌旁组织中的表达分布,并分析其表达的意义及表达之间的相关性。结果:URG4在肝癌组织及肝癌细胞系中的阳性表达率分别为48%和54%,而在正常组织中仅22.2%弱表达,其与HBx表达的相关系数分别为0.38和0.45(P0.05)。结论:URG4在肝癌组织及癌旁组织中的表达高于正常组织,且与HBx密切相关。     

LOXL4 is downregulated in hepatocellular carcinoma with a favorable prognosis

Lysyl oxidase like 4 (LOXL4), a member of the secreted copper-dependent amine oxidases that contribute to the assemble and maintenance of the extracellular matrix (ECM), was found to be up-regulated or down-regulated in different cancer types, suggesting its paradoxical roles in cancer. The specific role of LOXL4 in hepatocellular carcinoma (HCC), however, is still yet to be defined. Twenty-eight pairs of HCC specimens were used for LOXL4 mRNA expression analysis. The mRNA expression in HCC cell lines was examined, and HepG2 was selected for LOXL4 small interfering RNA (siRNA) interference to investigate the biological function of LOXL4, LOXL4 immunohistochemical staining was performed using a tissue microarray containing 298 HCC patients. The prognostic and diagnostic value of LOXL4 was evaluated using Cox regression and Kaplan-Meier analysis. LOXL4 mRNA or protein expression was significantly lower in HCC tissues than peritumoral tissues (LOXL4 mRNA expression, P = 0.018; LOXL4 protein expression, P < 0.001). Low LOXL4 expression was associated with lower overall survival (OS) rates and higher cumulative recurrence rates. Multivariate analysis indicated that LOXL4 was an independent prognostic indicator for OS and time to recurrence (TTR). Our results revealed that LOXL4 was down-regulated in HCC and correlated with aggressive tumors and a worse clinical outcome. LOXL4 may be a potential biomarker to identify the HCC patients with a higher risk of recurrence.     

HBsAg阳性肝癌患者预后及病理因素与ALK基因表达的相关性研究

 目的:检测ALK基因在HBsAg阳性肝细胞癌患者中的表达,并分析其与临床特征及预后的相关性。方法:收集我院2005~2010年261例术后经病理确诊的HBsAg阳性肝癌患者肿瘤组织及癌旁组织标本,采用免疫组织化学法和FISH法对标本石蜡切片进行分析,检测ALK表达情况,并探讨其对HBsAg阳性肝癌患者临床病理因素和预后的影响。结果:在肿瘤组织中,免疫组织化学法和FISH法分别检测到ALK阳性表达率为44.8%和32.6%。免疫组化结果进一步显示ALK蛋白表达与患者性别、肿瘤数目和微转移密切相关(P<0.05),而与患者的年龄、AFP水平、肿瘤大小、临床分期等无关;ALK阳性患者总生存期和无进展生存期均明显低于阴性患者(P<0.01);多因素分析显示,ALK表达和微转移是对患者无进展生存期具有统计学显著性的预后因素。结论:ALK在HBsAg阳性肝癌组织表达状态与肝癌的生长和转移关系密切,可以作为反映肝癌生物学行为和判断预后的有效指标。