肝细胞癌的相关血清标志物

肝细胞癌(HCC)的早期诊断是其治疗的关键,HCC血清标志物的检测为其诊断提供了有利的方法,并且操作简单,敏感性高、特异性强。目前常用的血清标志物为AFP、AFPvariants、AFPmRNA、AFU、GGT、DCP、AIF、GPC3等。这些标志物的联合使用有助于HCC的诊断及预后判断。     

肝细胞癌肿瘤标志物的新进展

肝细胞癌(HCC)是最常见的恶性肿瘤之一,在中国其病死率居恶性肿瘤的第三位.肿瘤标志物的测定是早期诊断和监测复发的有效方法 ,近年来这方面的研究进展迅速,它可包括癌胚抗原和糖类抗原、酶和同工酶、基因和细胞因子等四大类.本文综述了它们在HCC诊断、疗效评价、预后判断以及复发监测等方面的研究进展,并介绍了一些近年新发现的一些肿瘤标志物,如白介素6、LAM4基因、NDRG1基因等.     

肝细胞癌的血清标志物

 肝细胞癌（HCC）是最常见的恶性肿瘤之一，大多数患者在得到诊断时已属病程晚期，预后通常较差，目前非手术治疗5年生存率为20 %。筛查手段包括对具有发展为HCC高风险的肝硬化患者每6个月进行一次甲胎蛋白（AFP）和超声检查。但是，AFP的敏感性和特异性较差，超声则高度依赖于操作者的经验。除AFP，可与植物性凝集素晶体反应的AFP，γ-脱羧基凝血酶原和一些其他的生化标志物（如磷脂酰肌醇聚糖-3，人类肝细胞生长因子和类胰岛素生长因子）已被提议作为HCC的标志物。此外，通过近来采用的技术如基因表达微量检测和蛋白类似物，新的HCC特异性标志物有望成为现实。然而这些标志物的临床适用性尚待进一步证实。     

肝细胞癌的血清标志物

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor with increasing incidence worldwid.Most of patients with HCC are diagnosed at a late stage.Threrfore,the prognosis of HCC patients is generally poor with a 5-year survival rate of 20% if withoutoperration. Screening strategies including α-fetoprotein (AFP) and ultrasound every 6 months in patients with liver cirrhosis,the major risk factor for HCC development, have been recommended to detect HCC at earlier stages amenable to effective treatment strateges.AFP, however,is a marker with poor sensitivity and specificity and the ultrasound is highly dependent on the operator's experience.Apart from AFP, lens culinaris agglutinin-reactive AFP and des-gamma carbexyprothrombin and several other biomarkers(e.g., glypican-3,human hepatocyte growth factor,and insulin-like growth factor) have been proposed as markers for HCC detection.In addition,with recently employed techniques,such as gene-expressing microarrays and proteomics,it is to be expected that new HCC-specific markers will become available in the near future.For all such proposed markers,however,the clinical usefulness has to be carefully evaluated and validated.     

肝细胞癌的血清标志物

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor with increasing incidence worldwid.Most of patients with HCC are diagnosed at a late stage.Threrfore,the prognosis of HCC patients is generally poor with a 5-year survival rate of 20% if withoutoperration. Screening strategies including α-fetoprotein (AFP) and ultrasound every 6 months in patients with liver cirrhosis,the major risk factor for HCC development, have been recommended to detect HCC at earlier stages amenable to effective treatment strateges.AFP, however,is a marker with poor sensitivity and specificity and the ultrasound is highly dependent on the operator's experience.Apart from AFP, lens culinaris agglutinin-reactive AFP and des-gamma carbexyprothrombin and several other biomarkers(e.g., glypican-3,human hepatocyte growth factor,and insulin-like growth factor) have been proposed as markers for HCC detection.In addition,with recently employed techniques,such as gene-expressing microarrays and proteomics,it is to be expected that new HCC-specific markers will become available in the near future.For all such proposed markers,however,the clinical usefulness has to be carefully evaluated and validated.     

异常凝血酶原和肝细胞癌

目前肝细胞癌（hepatocellular carcinoma,HCC)的诊断主要有影像学诊断和血清肿瘤标志物的检测。异常凝血酶原（des-gamma-carboxy-prothrombin,DCP)又被称为PIVKA－Ⅱ（protein induced by vitamin K absence or antagonist-Ⅱ），与AFP（alpha-fetoprotein)和AFP－L3（alpha-fetoprotein L3 fraction)一样被认为是一种很有价值的肝细胞癌血清肿瘤标志物。在HCC的检测诊断上，它们之间无明显相关关系，而表现为一定的互补性，结合影像学诊断，动态观测HCC高危（肝炎、肝硬化）人群，这些血清肿瘤标志物有助于HCC的早期发现，同时对HCC的手术疗效的评价、预后的估评有着一定的指导意义。     

肝细胞生长因子及其受体与肝细胞癌

肝细胞生长因子(HGF)是正常肝细胞增生的强促有丝分裂原。近年研究发现，HGF同样影响肝细胞癌的生物学行为，其受体(c-Met原癌基因编码蛋白)也与原发性肝癌关系密切，因此可能成为原发性肝癌新的诊断标志物和治疗靶点。     

肝癌早期血清标志物研究的新进展

肝细胞癌是世界范围最常见的恶性肿瘤之一,死亡率位居世界肿瘤死亡第二位,肿瘤标志物是诊断早期肝癌的有效手段之一。近年来各种新的肿瘤标志研究进展迅速,在诊断肝癌的敏感度、特异度或复发和预后的判断等方面各具优势,本文就以上最具代表性的肝癌标志物研究新进展进行综述。     

肝细胞癌与肝炎后肝硬化中多种肿瘤标志物的比较

目的探讨多种肿瘤标志物在肝细胞癌和肝炎后肝硬化中的表达情况。方法采用多种肿瘤标志物蛋白芯片检测系统测定85例肝细胞癌患者和92例肝炎后肝硬化患者血清中肿瘤标志物（CA199、CEA、CA242、FER、AFP、CA125、CA153）的水平,并比较各指标在两组间的差异情况。结果 7项肿瘤指标在肝细胞癌和肝炎后肝硬化中都有不同程度的阳性表达,且CA242和AFP在两组肝病间的比较有明显的统计学意义。结论多种肿瘤标志物的联合检测对肝细胞癌的诊断有较高的临床参考价值,适合于无明显症状的门诊患者的筛查和肿瘤高危人群的普查。     

血清α—L—岩藻糖苷酶诊断原发性肝细胞癌

目的通过观察血清α-L-岩藻糖昔酶（AFU）活性水平在原发性肝细胞癌（HCC）患者与肝硬化、肝炎及其他恶性肿瘤患者中的变化，评价其在HCC诊断中的价值。方法对44例HCC、18例肝硬化、36例肝炎和30例其他恶性肿瘤患者测定血清AFU活性水平。部分HCC患者曾经接受经导管肝动脉化疗栓塞术（TAE）。结果对照组平均血清AFU活性水平为150．39±35．34nKat／L，HCC组280．11±148．15nKat／L，肝硬化组、肝炎组及其他肿瘤组分别为248．89±68．82、196．67±79.61、168.93±49．89nKat／L。HCC组与对照组及肝炎组、其他肿瘤组之间存在明显差别，但与肝硬化组有部分重叠。结论AFU可作为肿瘤标志物用于诊断HCC与AFP及超声等联合参照应用。     

肝癌的新型肿瘤标志物

肝细胞癌是全球最常见的恶性肿瘤之一,并在最常见的肿瘤致死原因中位列第三。随着医学的发展,肝癌的诊疗手段已经取得明显的进步,但由于缺乏有效的早期诊断方式,往往使得早期肝癌患者无法得到及时的治疗。因此,开发有效的肝癌早期诊断手段也将是一个改善患者预后的合理途径。本文通过系统复习相关文献,总结了肝癌部分常用肿瘤标志物(如甲胎蛋白)以及新型肿瘤标志物的机制及意义。     

Serum c-erbB-2 protein is a useful marker for monitoring tumor recurrence of the breast

C-erbB-2 oncogene protein (ErbB-2/HER-2) overexpression is a prognostic marker of breast carcinoma. The purpose of this study was to evaluate serum ErbB-2 for monitoring tumor recurrence of operable breast carcinoma patients. The subjects were 86 breast carcinoma patients with stage I-IIIB. Sera were collected at preoperative and postoperative periods from 1996 to 2000. The cutoff value was set at 5.4 ng/ml for preoperative patients and at 6.5 ng/ml for postoperative patients. Twenty-nine patients (34%) had higher preoperative serum ErbB-2 levels (>or=5.4 ng/ml). A higher preoperative serum ErbB-2 was associated with higher clinical stage, larger tumor size, nodal metastasis, higher histologic grade and lymphatic invasion, but not with vascular invasion, hormonal receptor status or other tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3). As of April 2005, 27 patients (31%) had recurrence and 18 (62%) of them had a higher preoperative serum ErbB-2. Seventeen patients died of tumor progression. The recurrence-free survival rates at 7 years after breast surgery were 84% in 57 patients with a normal preoperative serum ErbB-2 and 41% in 29 patients with a higher preoperative serum ErbB-2 (p < 0.0001). The overall survival rates at 7 years were 93% and 55% (p < 0.0001), respectively. A multivariate analysis revealed that preoperative serum ErbB-2 was an independent prognostic factor for recurrence-free survival and overall survival in breast carcinoma patients. The specificities and sensitivities of postoperative tumor markers (CEA, CA15-3 and ErbB-2) were 91%, 100% and 85%, and 40%, 30% and 70%, respectively. Serum ErbB-2 is a preoperative prognostic marker and may be useful for monitoring tumor recurrence of the breast.     

Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma

BackgroundThe identification of new biomarkers to predict the aggressiveness of hepatocellular carcinoma (HCC) and supplement the current set of prognosis and treatment algorithms is an important clinical need. Extracellular microRNAs (miRNAs) circulating in the blood are a new class of highly promising disease markers.AimHere we investigated the prognostic potential of miR-1 and miR-122 in sera from patients with HCC.MethodsRNA was extracted from 195 sera of HCC patients and 54 patients with liver cirrhosis, obtained at the time of study enrolment. miR-1 and miR-122 levels were correlated with overall survival (OS), Cancer of the Liver Italian Program (CLIP) score, Barcelona Clinic Liver Cancer stage, clinical chemistry parameters and tumor specific treatment.ResultsPatients with higher miR-1 and miR-122 serum levels showed longer OS than individuals with lower miR-1 and miR-122 serum concentrations (hazard ratio [HR] 0.440, 95% confidence interval [CI] 0.233–0.831, P = 0.011 for miR-1 and HR 0.493, 95% CI 0.254–0.956, P = 0.036 for miR-122, respectively). Serum miR-1 and miR-122 concentrations did not differ significantly between patients with HCC and liver cirrhosis. An age-, sex-, tumor stage and treatment-adjusted multivariate Cox regression analysis revealed that miR-1 serum levels (HR 0.451, 95% CI 0.228–0.856, P = 0.015) were independently associated with OS, whereas serum miR-122 was not. miR-1 serum levels showed no relevant correlation with clinical chemistry liver parameters, whereas serum miR-122 correlated with clinical chemistry parameters of hepatic necroinflammation, liver function and synthetic capacity.ConclusionOur data indicate that serum miR-1 is a new independent parameter of OS in HCC patients and may therefore improve the predictive value of classical HCC staging scores.     

实时荧光定量PCR检测原发性肝癌中PRL-2基因的表达

Objective: To quantitatively detect the expression level of PRL-2 in primary hepatocellular carcinoma using real-time fluorescence quantitative PCR. Methods: Total RNA isolated from human HCC and liver tissue adjacent to the tumor was reversely transcribed into cDNA. Real-time fluorescence quantitative PCR (Q-PCR) method was used to analyze the expres-sion level of PRL-2 gene. Results: The Q-PCR method was performed successfully to precisely detect RNA level. PRL-2 was expressed in all portal vein tumor thrombosis (PVTT) and HCC, but only in some paratumor tissue. The highest expression level of PRL-2 gene was recorded in PVTT; meanwhile expression level of PRL-2 was higher than that in paratumor liver tis-sues and in HCC (P<0.01), and it was higher in HCC than that in paratumor liver tissues. Conclusion: The Q-PCR may be the most precise method to quantitatively detect RNA level and can be used in gene expression changes. The PRL-2 gene has higher expression in PVTT than that in HCC and in paratumor liver tissue cells, indicating that it plays an important role in the development and metastasis of the HCC.     

大肠癌患者血清基质金属蛋白酶-7含量的临床意义

目的:评估大肠癌患者血清MMP-7含量及其临床意义.方法:术前应用免疫酶联反应技术对50例大肠癌患者以及36例健康对照者的血清MMP-7含量进行检测,同时也检测这些患者血清CEA、CA19-9以及CA24-2含量.将大肠癌患者的血清MMP-7及其它肿瘤标志物的含量与健康对照者进行了比较.对不同临床病理分期的大肠癌患者血清MMP-7含量进行评估.结果:研究发现多数大肠癌患者的血清MMP-7含量升高.大肠癌患者的血清MMP-7含量,分布范围0.72-28.69ng/ml(平均4.41ng/ml;中位4.19ng/ml),显著高于健康对照者,分布范围0.69-3.97ng/ml(平均1.62ng/ml;中位1.36ng/ml)(P<0.01).大肠癌患者的血清MMP-7平均阳性率(46%)与CEA(30%),CA19-9(26%)及CA24-2(24%)相比均升高(P<0.05).进展期肿瘤患者血清MMP-7含量显著高于早期肿瘤患者(P<0.05).结论:血清MMP-7有可能成为大肠癌患者临床监测标志物.     

大肠癌患者血清基质金属蛋白酶-7含量的临床意义

目的：评估大肠癌患者血清MMP-7含量及其临床意义.方法：术前应用免疫酶联反应技术对50例大肠癌患者以及36例健康对照者的血清MMP-7含量进行检测,同时也检测这些患者血清CEA、CA19-9以及CA24-2含量.将大肠癌患者的血清MMP-7及其它肿瘤标志物的含量与健康对照者进行了比较.对不同临床病理分期的大肠癌患者血清MMP-7含量进行评估.结果：研究发现多数大肠癌患者的血清MMP-7含量升高.大肠癌患者的血清MMP-7含量,分布范围0.72-28.69ng/ml（平均4.41ng/ml;中位4.19ng/ml）,显著高于健康对照者,分布范围0.69-3.97ng/ml（平均1.62ng/ml;中位1.36ng/ml）（P〈0.01）.大肠癌患者的血清MMP-7平均阳性率（46%）与CEA（30%）,CA19-9（26%）及CA24-2（24%）相比均升高（P〈0.05）.进展期肿瘤患者血清MMP-7含量显著高于早期肿瘤患者（P〈0.05）.结论：血清MMP-7有可能成为大肠癌患者临床监测标志物.