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| 1 | Specific molecular markers in hepatocellular carcinoma显示文摘BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to September 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development and metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-β1, HS-GGT, and free insulin-like growth factor (IGF)-Ⅱ may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-β1-mRNA, IGF-Ⅱ-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are usefulto early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC. | Yao, Deng-Fu Dong, Zhi-Zhen Yao, Min | 2007 | Hepatobiliary & Pancreatic Diseases International2007，6，3： | 55 |
| 2 | 肝细胞癌生物标志物的研究进展显示文摘原发性肝癌(primaryhepaticcancer,PHC)是世界范围内第8位最常见的恶性肿瘤,在我国肝细胞癌(hepatocellularcarcinoma,HCC)占其91.5%.HCC是肿瘤病因学中的重要类型,肝硬化、病毒性肝炎、化学致癌物及环境因素等所造成的慢性肝脏损害都可诱发HCC.HCC恶性度高,容易复发及转移,预后差,而且早期诊断较困难,延误了最佳治疗时期.HCC的生物标志物对于HCC的早期诊断、监测肿瘤进展、疗效判定、复发和存活率的判定十分重要.因此,寻找有效的HCC生物标志物是医学工作者多年以来的努力方向,并取得了很大的进展.甲胎蛋白(alpha-fetoprotein,AFP)是临床上诊断HCC最常用的指标,其敏感性和特异性分别为60%和90%,AFP-L3、AFU、DCP及anti-p53等也都有各自的优缺点,新近发现SCCA-IgMIC在HCC患者有表达,其敏感性及特异性均较高,可能不久以后会成为HCC早期诊断的重要依据. | 王嘉倍 刘连新 | 2005 | 世界华人消化杂志2005，13，18： | 34 |
| 3 | Overexpression of insulin-like growth factor-Ⅰ receptor as a pertinent biomarker for hepatocytes malignant transformation显示文摘AIM:To investigate the dynamic features of insulinlike growth factor-Ⅰreceptor(IGF-ⅠR)expression in rat hepatocarcinogenesis,and the relationship between IGF-ⅠR and hepatocytes malignant transformation at mRNA or protein level.METHODS:Hepatoma models were made by inducing with 2-fluorenylacetamide(2-FAA)on male SpragueDawley rats.Morphological changes of hepatocytes were observed by pathological Hematoxylin and eosin staining,the dynamic expressions of liver and serum IGF-ⅠR were quantitatively analyzed by an enzymelinked immunosorbent assay.The distribution of hepatic IGF-ⅠR was located by immunohistochemistry.The fragments of IGF-ⅠR gene were amplified by reverse transcription-polymerase chain reaction,and confirmed by sequencing.RESULTS:Rat hepatocytes after induced by 2-FAA were changed dynamically from granule-like degeneration,precancerous to hepatoma formation with the progressing increasing of hepatic mRNA or IGF-ⅠR expression.The incidences of liver IGF-ⅠR,IGF-ⅠR mRNA,specific IGF-ⅠR concentration(ng/mg wet liver),and serum IGF-ⅠR level(ng/mL)were 0.0%,0.0%,0.63±0.17,and 1.33±0.47 in the control;50.0%,61.1%,0.65±0.2,and 1.51±0.46 in the degeneration;88.9%,100%,0.66±0.14,and 1.92±0.29 in the precancerosis;and 100%,100%,0.96±0.09,and2.43±0.57 in the cancerous group,respectively.IGF-ⅠR expression in the cancerous group was significantly higher(P<0.01)than that in any of other groups at mRNA or protein level.The closely positive IGF-ⅠR relationship was found between livers and sera(r=0.91,t=14.222,P<0.01),respectively.CONCLUSION:IGF-ⅠR expression may participate in rat hepatocarcinogenesis and its abnormality should be an early marker for hepatocytes malignant transformation. | Xiao-Di Yan Min Yao Li Wang Hai-Jian Zhang Mei-Juan Yan Xing Gu Yun Shi Jie Chen Zhi-Zhen Dong Deng-Fu Yao | 2013 | World Journal of Gastroenterology2013，19，36： | 16 |
| 4 | 原发性肝癌中多项肿瘤标志物检测的临床意义显示文摘目的:探讨检测血清GGT、GGT-Ⅱ、AFP在诊断原发性肝癌中的临床意义。方法:选择原发性肝癌30例、肝硬化40例、病毒性肝炎45例、肝损伤6例和正常对照者32例。血清GGT、GGT-Ⅱ、AFP分别采用化学免疫分析法、不连续缓冲系统聚丙烯酰胺凝胶垂直电泳检测法和自动生化仪进行检测。结果:原发性肝癌组GGT为(281±198)U/L,AFP为(3167±867)μg/L,明显高于肝硬化组[GGT:(203±135)U/L,P<0.05;AFP:(403±274)μg/L,P<0.01]、病毒性肝炎组[GGT:(173±125)U/L,P<0.05;AFP:(102±95)μg/L,P<0.01]、肝损伤组[GGT:(401±212)U/L,AFP:(16±14)μg/L,P<0.01]及正常对照者组[GGT:(26.0±5.1)U/L,P<0.05;AFP:(2.1±1.0)μg/L,P<0.01];诊断原发性肝癌的特异性AFP最高为(91%),灵敏度最高为GGT-Ⅱ(93%);若将三者联合检测,诊断原发性肝癌的灵敏度可达96%。结论:肿瘤标志物的联合检测可提高原发性肝癌的诊断率。 | 鲁亮 李杭 张汉群 曹辉 罗旻 | 2014 | 现代肿瘤医学2014，22，3： | 12 |
| 5 | 外周血磷脂酰肌醇蛋白聚糖-3检测在原发性肝癌诊断中的意义显示文摘目的探讨外周血磷脂酰肌醇蛋白聚糖-3(GPC3)检测在原发性肝癌诊断中的意义。方法应用酶联免疫吸附试验检测80例原发性肝癌患者、78例肝内良性占位病变患者和40例健康对照者外周血GPC3蛋白水平,了解GPC3蛋白在各组中的阳性率,探讨GPC3蛋白诊断原发性肝癌的敏感性和特异性。结果健康对照组血清GPC3蛋白水平为(196.76±112.24)pg/mL,肝内良性占位组为(248.56±123.35)pg/mL,原发性肝癌组为(678.23±325.22)pg/mL。原发性肝癌组血清GPC3蛋白水平高于肝内良性占位组和正常对照组(F=18.76,P<0.01)。根据ROC曲线,若外周血GPC3蛋白诊断原发性肝癌的界值为412.6 pg/mL,则敏感度为63.2%,特异度为89.3%,健康对照者GPC3蛋白阳性率为2.50%,肝内良性占位病变组阳性率为14.1%,原发性肝癌组阳性率为65.0%。各组间血清GPC3蛋白阳性率统计学差异有显著性意义(χ2=40.28,P<0.01)。若AFP诊断肝癌的截止值为400 ng/mL,AFP的阳性率为46.3%,联合检测AFP和GPC3的阳性率提高至77.5%。结论 GPC3蛋白可作为原发性肝癌诊断及鉴别诊断的重要指标之一。联合检测GPC3和AFP可能提高原发性肝癌的诊断敏感性。 | 吴诗品 刘真真 杨智 | 2010 | 中国现代医学杂志2010，20，21： | 6 |
| 6 | 血清标志物在肝细胞癌诊断中的应用显示文摘肝细胞癌(Hepatocellular carcinoma,HCC)是临床上最常见的恶性肿瘤之一,全球发病率和死亡率逐年增长,发病率居于恶性肿瘤的第5位,死亡率位居肿瘤相关死亡的第3位[1].全球每年大约有600 000新增患者,并有超过500 000名患者死于肝细胞癌[2]. | 朱桂婷 娄国强 施军平 | 2010 | 中华实验和临床病毒学杂志2010，，6： | 5 |
| 7 | 肝癌实验室诊断研究进展显示文摘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。肝癌的诊断特别是早期诊断,对于提高患者生存率至关重要。我们简要综述了国内外肝癌实验室诊断中的常用标志物以及检测方法的进展,并展望了其发展前景。 | 常林 杨瑞丽 | 2010 | 生物技术通讯2010，21，1： | 3 |
| 8 | 基因表达异常与肝癌诊断、转移及复发监测显示文摘肝细胞癌(HCC)预后极差,延长患者生存期的关键是早期诊断和早期手术治疗。甲胎蛋白(AFP)作为肝癌标志,存在较高的假阳性和假阴性。新的基因标志可与AFP互补诊断,有助于肝癌诊断及转移、术后复发的监测。本文重点评价了基因标志在肝癌诊断及转移、复发监测中的应用与前景。 | 姚登福 | 2007 | 南通大学学报(医学版)2007，27，4： | 3 |
| 9 | 基因标志物在肝癌诊断中的临床价值显示文摘肝癌的发生与肝炎病毒感染、致癌物作用、癌基因或癌相关基因激活、抗癌基因失活或胚胎期某些癌基因重新复活等诸多因素有关,并经启动、促进、演变多阶段的发病过程。临床匕肝癌确诊时已多属中、晚期,缺乏有效治疗,术后易复发及远处转移,预后较差,早诊断、早治疗至关重要。早期诊断和术后复发监测仍是临床研究的重点。 | 姚登福 姜华 | 2007 | 中华肝脏病杂志2007，15，8： | 2 |
| 10 | 熊去氧胆酸对肝癌模型大鼠γ-谷氨酰转移酶基因表达的影响显示文摘目的探讨熊去氧胆酸(UDCA)对肝癌模型大鼠γ-谷氨酰转移酶(γ-GGT)基因亚型表达的影响。方法采用逆转录聚合酶链反应PCR检测正常组及肝癌模型组大鼠的不同癌变肝组织及其血液GGT mRNA亚型(F、H、P)的表达情况。对比正常组,UDCA实验A、B组和对照组大鼠GGT mRNA亚型的表达情况。结果癌组织中的GGT mRNA的F亚型阳性检出率显著小于正常肝组织、非肝癌肝组织及癌周组织(P<0.01);癌组织、癌周组织的H亚型阳性检出率均高于正常肝组织及非肝癌肝组织(P<0.01或P<0.05)。UDCA实验A、B组的不同肝组织及血液的GGT mRNA-H亚型的表达量均较模型组明显下降(P<0.05);UDCA实验A、B组癌组织F亚型的表达量较模型组显著降低(P<0.05)。结论在大鼠的肝癌发生过程中存在着GGT mRNA由F亚型向H亚型的转变。UDCA能减少GGT mRNA-H亚型的表达,间接反映UDCA能减少肝癌的发生,对肝癌的发生有一定的预防作用。 | 盛瑜 韩国庆 秦成勇 任万华 刘慧 王夏青 | 2012 | 胃肠病学和肝病学杂志2012，21，7： | 2 |
| 11 | Implantation of a drug delivery system during surgery for patients with primary hepatocarcinoma显示文摘BACKGROUND: Postoperative regional chemotherapy is one of the most effective methods to decrease the recurrent rate and improve the prognosis of primary hepatocarcinoma (PHC). This study was undertaken to assess the optimal pathway to implant the drug delivery system (DDS) in the different ways of resecting PHC so as to offer a valuable reference to clinical implantation of the DDS. METHODS: One hundred and ninety cases were divided into two groups according to whether the tumors were resected completely (A) or not (B). Groups A and B were subdivided into three groups a, b and c according to the pathway selected for DDS implantation. The patients in subgroup a received DDS implantation through both the hepatic artery and portal vein (A+P-implanted group), the patients in subgroup b received DDS implantation through the portal vein (P-implanted group), and the patients in subgroup c received DDS implantation through the hepatic artery (A-implanted group). RESULTS: The 1- and 3-year recurrent rates of subgroup c in group A were higher than those of subgroup b, and there was no significant difference between subgroups a and b. Compared with subgroups a and c, the 1- and 3-year survival rates of subgroup b were similar to those of group a but higher than those of group c. The 1- and 3-year survival rates between subgroups a and b in group B were significantly different. The prognosis of subgroup c was lower than that of subgroup a and no significant difference was observed between subgroups b and c. CONCLUSIONS: The DDS should be implanted into the portal vein when PHC is resected completely. It may be better to implant it into both portal vein and hepatic artery if the tumor cannot be completely resected. | Wan-Ping Chen, Xin He, Qi-Fa Ye and Ke Li Institute of Organ Transplantation, Third Xiangya Hospital, Xiangya Medical College, Central South University, Changsha 410013, China, and Institute of Clinical Pharmacology, Xiangya Medical College, Central South University, Changsha 410078, China | 2006 | Hepatobiliary & Pancreatic Diseases International2006，5，3： | 2 |
| 12 | Abnormal expression of hepatomas and circulating telomerase and its clinical values显示文摘BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Te-lomerase is reactivated in various types of malignant tumors and may contribute to the development of HCC. To evaluate the role of telomerase in formation and development of HCC, we analyzed its expression status in different parts of HCC tissues and peripheral blood mono-nuclear cells (PBMCs) , and explored its clinical implications for diagnosis of HCC. METHODS: Total RNAs and telomerase were extracted from HCC and their non-cancerous tissues, and both relationships were analyzed between them. The expression of telomerase reverse transcriptase (hTERT) mRNA and telomerase activities in liver tissues and PBMCs were detected by RT-PCR and telomeric repeat amplification protocol (TRAP)-ELISA, respectively. The diagnostic values of telomerase in PBMCs were investigated in the diagnosis and differentiation of HCC. RESULTS: The specific activities of telomerase were 18.25 ±15.02 A/μg RNA in HCC tissues, and significantly higher than those in their non-cancerous tissues (8.16 ± 6.22 A/μg RNA, P <0. 05). But total RNA levels in HCC were 12.40 ±7.34 μg/mg wet liver and lower than 53.77 ± 52.02 μg/mg wet liver in their non-cancerous parts (P < 0.01). The different telomerase levels could be detected in PBMCs from patients with chronic liver diseases and control group. The enzyme activities were significantly higher in HCC than in any other groups (P <0.01). However, circulating telomerase levels were more obviously decreased in HCC patients after transcatheter arterial embolization treatment than before the treatment (P <0.01). The analysis of combined serum alpha-fetoprotein level and PBMCs telomerase was more sensitive and specific for the diagnosis of HCC. CONCLUSION: The abnormal expression of telomerase in HCC tissues and circulating PBMCs could be a useful marker to the diagnosis and prognosis of HCC. | Wei Wu, Deng-Fu Yao, Li-Wei Qiu, Xin-Hua Wu, Ming Yao, Xiao-Qin Su and Li Zou Nantong, China Research Center of Clinical Molecular Biology, Affiliated Hospital, Nantong University, Nantong 226001, China | 2005 | Hepatobiliary & Pancreatic Diseases International2005，4，4： | 1 |
| 13 | GGT亚组分及基因亚型与肝癌的特异性诊断显示文摘肝病及肝外肿瘤患者血γ-谷氨酰移换酶(GGT,EC 2.3.2.2)总活性均异常,肝癌患者血清经聚丙烯酰胺梯度凝胶电泳,可将GGT分出十多种亚组分(Ⅰ,Ⅰ′,Ⅱ,Ⅱ′,β,δ,ε,φA,ⅦB,φC,γA,γB),而其中Ⅰ′,Ⅱ,Ⅱ′为肝癌所特有,被称为肝癌特异性GGT(HS-GGT).肝GGT基因表达与肝癌发展密切相关,其基因亚型有胎肝型(F)、胎盘型(P)和肝癌细胞型(H),基因型H主要见于肝癌组织.众多的基础及临床研究证实HS-GGT和基因H亚型为肝癌特异标志,具有较高的特异性和敏感性,其分析有助于肝癌诊断与鉴别. | 姚登福 董志珍 顾青青 姚敏 | 2007 | 世界华人消化杂志2007，15，36： | 1 |
| 14 | 肝肿瘤标志物及临床检测应用显示文摘肿瘤标志物AFP、AFP variants、AFPmRNA、CEA、HCCR、SCCA-IgMIC、DCP、AFU、GPC3、GGT、VEGF在肝肿瘤不同发展阶段含量有显著差异。选择特异性强、敏感度高的肿瘤标志物对肝肿瘤的诊断治疗至关重要。目前肿瘤标志物联合测定仍为肝肿瘤诊断的最好手段。 | 雍刘军 张星宇 | 2009 | 成都医学院学报2009，4，3： | 1 |
| 15 | 重视分子标志物对肝癌早期诊断和转移与复发监测的价值显示文摘 | 姚登福 孟宪镛 | 2005 | 胃肠病学和肝病学杂志2005，14，6： | 1 |
| 16 | 比较两种方法检测GGT-Ⅱ对肝细胞肝癌的诊断价值显示文摘目的比较两种方法检测γ-谷氨酰转移酶同工酶Ⅱ(GGT-Ⅱ)对肝细胞肝癌的诊断价值。方法使用传统实验室自配试剂聚丙烯酰胺凝胶电泳(PAGE)手工法和商品化试剂盒PAGE法检测GGT-Ⅱ,检测113例肝细胞肝癌、51例肝硬化、21例慢性肝炎及30例健康对照组血清样本中GGT-Ⅱ。结果传统手工法检测GGT-Ⅱ较之试剂盒法费时费力,完成全程检测时间(26.5±2.5)h明显多于试剂盒法(6.5±0.5)h,差异有统计学意义(P<0.05);手工法平均重现率(94.4%)相比于试剂盒法(100%),差异无统计学意义(P>0.05)。试剂盒法在肝细胞肝癌组GGT-Ⅱ检出敏感度(84.1%)相比于手工法(74.3%),但差异无统计学意义(P>0.05)。结论商品化PAGE提供了一个简单、重复性好的GGT-Ⅱ检测方法,且对肝细胞肝癌有较好的诊断敏感度。 | 尤小燕 吴建华 江枫 | 2017 | 国际检验医学杂志2017，38，24： | 0 |
| 17 | 循环血AFP-mRNA与HS-GGT检测对肝癌的诊断与监测价值(英文)显示文摘Objective: Early finding of hepatocellular carcinoma(HCC) and monitoring of its metastasis are of the utmost importance. The objectives of this study were to investigate the values of circulating hepatoma-specific gamma-glutamyl transferase(HS-GGT) fraction and α-fetoprotein mRNA(AFP-mRNA) from peripheral blood mononuclear cells(PBMCs) in diagnosis or monitoring metastasis of HCC. Methods: Total RNA was extracted from hepatomas or PBMCs of patients, synthesized to AFP-cDNA through random primers and reverse transcriptase, amplified by using a nested PCR assay, and confirmed by sequencing. Simultaneity, the HS-GGT activities were quantitatively determined in sera of patients. The comprehensive assessments of two markers were investigated in HCC patients. Results: The amplified fragments of AFP-mRNA were identical to original designed ones(159 bp) and confirmed by sequencing. The lowest sensitivity was 2 ng/L of total RNA. The incidences of AFP-mRNA and HS-GGT were 60.4%(113 of 187) and 84.5%(158 of 187) in the HCC group, and their significantly higher(P < 0.01) than that in any of other groups. The high frequencies of HS-GGT and AFP-mRNA were 78.2% and 56.4% in the HCC patients with AFP < 50 ng/mL. All positive of AFP-mRNA was found in HCC patients with extrahepatic metastasis. No significant correlation was found between tumor size and AFP-mRNA or HS-GGT. The total incidence of combined AFP-mRNA and HS-GGT detection was 93.6 % for HCC diagnosis. Conclusion: HS-GGT and AFP-mRNA are specific markers for HCC diagnosis or differentiation, especially the former for early finding and the later for monitoring metastasis of HCC. | Li Wang Min Yao Yao Yao Liuhong Pan Shaolin Lu Dengfu Yao | 2014 | The Chinese-German Journal of Clinical Oncology2014，13，10： | 0 |
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