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。     

肝细胞癌患者血清中Talin1的表达及其临床意义

目的检测肝细胞癌(HCC)患者血清Talin1的水平,评估其在HCC临床诊断中的价值。方法收集40例HCC患者、30例肝硬化(LC)患者、30例健康对照者(HC)的静脉血,分离血清,采用酶联免疫吸附试验(ELISA)检测血清中Talin1的水平,并与常规检测血清甲胎蛋白(AFP)的结果进行比较。应用受试者工作特征曲线分析Talin1相对于AFP在HCC中的诊断价值。结果HCC患者血清Talin1的水平明显高于LC和HC组(P<0.001)。在诊断HCC的敏感度、特异度、阳性预测值和阴性预测值等方面,Talin1的诊断精确性高于AFP。结论 Talin1是一种新型的诊断标志物,可以用于HCC的临床诊断,其敏感度和特异度高于传统的诊断标志物AFP。     

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。     

肝癌患者血清α—L—岩藻糖苷酶活力与肿瘤大小关系的研究

B超和CT是原发性肝癌（HCC）的主要影像学诊断方法，但B超难以检出等回声光团的小肝癌患者。血清AFP水平是HCC的重要标志物，但大约40％的早期HCC和15％～20％的进展期HCC患者AFP水平正常[1]，故也不是检测小HCC最敏感的指标。近年来研究发现血清α－L－岩藻糖昔酶（AFU）活力是诊断HCC有用的指标[2]，但其活力是否也像AFP一样与肿瘤大小有关，尚不清楚。本文旨在评价HCC患者血清AFU活力与肿瘤大小的关系。1材料与方法1．1研究对象52例HCC患者，平均年龄55．8±13．7岁；男40例，女12例，诊断依据主要为B超、CT、血清AF…     

异常凝血酶原和肝细胞癌

目前肝细胞癌 (hepatocellularcarcinoma ,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 (proteininducedbyvita minKabsenceorantagonist II) ,与AFP(alpha fetoprotein)和AFP L3(alpha fetoproteinL3fraction)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     

血清AFP、GP73、GPC3单独及联合检测对肝细胞癌的诊断价值

目的探讨血清中AFP、GP73、GPC3三种肿瘤标志物在肝细胞癌(hepatocellular carcinoma,HCC)中的诊断价值及联合检测的意义。方法检测了45例HCC患者、32例乙肝携带者和30例正常体检者血清中AFP、GP73、GPC3的含量并进行相关分析。结果 AFP、GP73、GPC3用于诊断HCC时的敏感度和特异度分别是57.8%和90.6%、80.0%和98.3%、31.1%和92.3%,ROC曲线下面积分别为0.874、0.963、0.507;AFP与GP73联合,AFP与GPC3联合,GP73与GPC3联合以及三种标志物联合时敏感度和特异度分别是93.9%和88.9%、73.3%和83.8%、84.4%和91.5%、95.6%和82.1%,ROC曲线下面积分别为0.976、0.821、0.963、0.976。结论联合检测血清中AFP和GP73对HCC的诊断具有重要价值,血清GPC3检测对HCC的诊断意义较小。     

肝细胞癌标志物去γ—羧基凝血酶原研究进展

去γ—羧基凝血酶原(DCP)是肝细胞癌(HCC)的一种标志物，对HCE的诊断特异性超过甲胎蛋白(AFP)达95％以上，但其敏感性低于AFP。DCP不仅可用于HCC的诊断，也可用于对HCC的复发、转移及预后判断。随着研究的不断深入，DCP将会在HCC的早期发现、早期诊断以及预后判断中发挥更大作用。     

β-HCG与肝细胞癌的相关性研究

目的评估人绒毛膜促性腺激素（β-HCG）检测在肝细胞癌（HCC）诊断和预后中的价值。方法用微粒子酶免发光技术（MEIA）测定83例HCC患者，25例肝硬化患者和62名正常人血清的5种HCC血清标志物，包括β-HCG、甲胎蛋白（AFP）、糖链抗原19—9（CA19—9）、糖链抗原125（CA125）、癌胚抗原（CEA）。结果通过5种血清学指标检测，HCC患者5种血清学指标与肝硬化组和正常人组比较差异均有显著性（P〈0．01），β-HCG和AFP在Ⅰ期HCC和Ⅰ、Ⅲ期HCC中表达差异无显著性。部分AFP阴性患者β-HCG可阳性。结论β-HCG检测可提高HCC早期诊断率，同时，也可能为HCC生物治疗提供一个新的靶点。     

去γ-羚基凝血酶原对原发性肝细胞癌的诊断价值

目的:探讨血清肿瘤标志物去γ-羧基凝血酶原(des-γ-carboxy prothrombin,DCP)对原发性肝细胞癌(hepatocellularcarcinoma,HCC)的诊断价值.方法:172例研究对象分为正常对照组(25例)、慢性肝炎组(20例)、肝硬化组(51例)及HCC组(76例),用酶联免疫法(EusA)测定血清DCP浓度,同时用电化学发光免疫法(ECLIA)测定血清AFP浓度,对比分析DCP、AFP及两者联合检测对HCC患者诊断的灵敏度、特异度和准确度,并对HCC病灶大小、门静脉癌栓浸润及背景肝病等临床病理特征与DCP、AFP作相关性分析.结果:正常对照组、慢性肝炎组、肝硬化组及HCC组的DCP平均浓度分别为17.72±9.59、26.12±12.64、37.45±18.26和806.71±639.79mAU/ml,可见DCP浓度在四组间呈递增趋势(P<0.05),且HCC组DCP浓度显著高于其它三组(P<0.01).正常对照组、慢性肝炎组、肝硬化组及HCC组AFP平均浓度分别为7.93±5.42、14.59±11.91、16.29±14.10和547.47±544.98ng/ml,HCC组AFP浓度也明显高于其它三组(P<0.01).统计分析显示血清DCP、AFP对HCC诊断阳性率分别为78.95%、73.68%,而两项联合使用对HCC诊断阳性率提高至89.47%.较大病灶(>5cm)、门静脉癌栓(PVI)阳性HCC患者的DCP浓度高于小病灶、PVI阴性HCC患者;HBSAg阳性HCC患者DCP浓度高于HBSAg阴性HCC患者.结论:DCP对HCC具有较好的诊断价值,其浓度与HCC的病灶大小、门静脉癌栓浸润等临床病理特征相关,且不受HBV感染的影响,适用于我国以HBV感染为背景肝病的HCC诊断.其灵敏度及特异度较AFP高.联合DCP、AFP检测能明显提高HCC的诊断率.     

肝细胞癌标志物去γ-羧基凝血酶原研究进展

去γ-羧基凝血酶原(DCP)是肝细胞癌(HCC)的一种标志物,对HCC的诊断特异性超过甲胎蛋白(AFP)达95%以上,但其敏感性低于AFP.DCP不仅可用于HCC的诊断,也可用于对HCC的复发、转移及预后判断.随着研究的不断深入,DCP将会在HCC的早期发现、早期诊断以及预后判断中发挥更大作用.     

Development of a novel assay to quantify serum human telomerase reverse transcriptase messenger RNA and its significance as a tumor marker for hepatocellular carcinoma

Currently available tumor markers for hepatocellular carcinoma (HCC) are alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and Des-gamma-carboxy prothrombin (DCP). However, their positive rate can not surpass abdominal ultrasonography (US) as modalities to detect small HCC at early stage, resulting in a possible delay of its diagnosis. There is a need to develop an additional sensitive marker to improve the early detection of HCC. We here introduced a newly developed quantitative detection method for serum hTERT mRNA, which has a clinical significance in HCC diagnosis. Briefly, we examined its sensitivity and specificity in HCC diagnosis, clinical significance in comparison with other tumor markers, and its correlations with the clinical parameters. Serum hTERT mRNA showed higher values in patients with HCC than those with chronic liver diseases. hTERT mRNA expression independently correlated with clinical parameters such as differentiation degree (p < 0.001). The sensitivity/specificity of hTERT mRNA in HCC diagnosis showed 88.2/70.0%. hTERT mRNA proved to be expectedly superior to AFP mRNA , AFP and DCP in HCC diagnosis. Importantly, hTERT mRNA in serum correlated with that in HCC tissue. Thus, we report that serum hTERT mRNA is a novel and available marker for HCC diagnosis.     

Application of Joint Detection of AFP,CA19-9, CA125 and CEA in Identification and Diagnosis of Cholangiocarcinoma

Objective: To explore the application of joint detection of serum AFP, CA19-9, CA125 and CEA in identificationand diagnosis of cholangiocarcinoma (CC). Materials and Methods: The levels of serum AFP, CA19-9, CA125and CEA of both 30 patients with CC and 30 patients with hepatocellular carcinoma (HCC) were assessed.Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic effects of single and jointdetection of those 4 kinds of tumor markers for CC. Results: The levels of serum CA19-9, CA125 and CEAin CC patients were higher than that in HCC patients,whereas that of serum AFP was significantly lower s.The area under ROC curve of single detection of serum AFP, CA19-9, CA125 and CEA were 0.05, 0.86, 0.84and 0.83, with the optimal cutoff values of 15.4 ng/ml, 125.1 U/ml, 95.7 U/ml and 25.9 ng/ml, correspondingly,and the percentage correct single diagnosis was <79%. With joint detection, the diagnostic effect of combinedAFP, CA19-9, CA125 and CEA was the highest, with an area under the ROC curve of 0.94 (95%CI 0.88~0.99).Conclusions: Single detection of serum CA19-9, CA125 and EA is not meaningful. The sensitivity, specificity,the rate of correct diagnosis and the area under ROC curve of joint detection of AFP, CA19-9, CA125 and CEAare highest, indicating that the joint detection of these 4 tumor markers is of great importance in the diagnosisof CC.     

3种肿瘤标记物联合检测对肝细胞癌切除术后再次复发的预测价值

目的：研究肿瘤标记物α-甲胎蛋白（AFP）、甲胎蛋白抑制体（AFP-L3）及脱-γ-羧基-凝血酶原（DCP）对肝细胞癌（ HCC）患者行肝切除术后复发的预测价值。方法收集行HCC肿瘤病灶根治性切除术的患者58例,考察患者的基本情况以及血清DCP、AFP及AFP-L3水平与HCC术后复发率的关系。结果术后血清AFP、DCP及AFP-L3水平均升高的患者复发率均明显提高。多因素分析结果显示：HCC患者肝切除术前血清AFP、DCP及AFP-L3联合检测与术后复发率无相关性[1．13（0．804～1．479）,P＞0．05],而术后血清AFP、DCP及AFP-L3联合检测则是影响术后复发率的独立因素[3．68（1．711～3．798）,P＜0．01]。结论血清中肿瘤标记物AFP、DCP及AFP-L3联合检测对HCC患者肝切除术后复发监测敏感有效,为HCC术后疗效评估及追踪复查提供了一条新途径。     

Enhanced detection of hepatocellular carcinoma.

BACKGROUND: Tumor markers in the early detection of tumors are promising tools that could improve the control and treatment of tumors. While alpha-fetoprotein (AFP) is a commonly used tumor marker in the detection of hepatocellular carcinoma (HCC), its sensitivity and specificity are insufficient to detect HCC in all patient samples. METHODS: We compared AFP with serum levels of vascular endothelial growth factors (VEGF and VEGF-A), insulin-like growth factor-2 (IGF-II), and the activity of the lysosomal enzyme alpha-L-fucosidase (AFU) in the sensitivity of detection of HCC and cirrhosis in Egyptian patients. RESULTS: The sensitivity of tumor detection using AFP was 68.2%. This level of detection was increased to 88.6% when AFP was evaluated in conjunction with AFU. The combined use of AFP and VEGF increased the sensitivity of detection to 95.5% in patients with HCC. The combination of the three markers yielded 100% detection sensitivity. VEGF-A showed a low specificity (20%), and IGF-II showed extremely low sensitivity (4.5%). CONCLUSIONS: We suggest that AFU or VEGF or both be measured with AFP to improve the detection sensitivity of HCC.     

Can Glypican3 be Diagnostic for Early Hepatocellular Carcinoma among Egyptian Patients?

Background: Because of the high prevalence of hepatocellular carcinoma (HCC) in Egypt, new markerswith better diagnostic performance than alpha-feto protein (AFP) are needed to help in early diagnosis. Theaim of this work was to compare the clinical utility of both serum and mRNA glypican3 (GPC3) as probablediagnostic markers for HCC among Egyptian patients. Materials and Methods: A total of 60 subjects, including40 with HCC, 10 with cirrhosis and 10 normal controls were analyzed for serum GPC3 (sGPC3) by ELISA.GPC-3 mRNA from circulating peripheral blood mononuclear cells was amplified by RT-PCR. Both markerswere compared to some prognostic factors of HCC, and sensitivity of both techniques was compared. Results:Serum glypican-3 and AFP were significantly higher in the HCC group compared to cirrhotic and normal controls(p<0.001). Sensitivity and specificity were (95% each) for sGlypican-3, (82.5% and 85%) for AFP, and (100% and90%) for Glypican3 mRNA , and (80% and 95%) for double combination between sGPC3 and AFP respectively.Conclusion: Both serum GPC-3 and GPC-3mRNA are promising diagnostic markers for early detection of HCCin Egyptian patients. RT- PCR proved to be more sensitive (100%) than ELISA (95%) in detecting glypican3.     

去γ-羧基凝血酶原在原发性肝癌中的应用

去γ-羧基凝血酶原(DCP)与甲胎蛋白(AFP)一样被认为是一种很有价值的肝癌血清肿瘤标志物.DCP作为肝癌的肿瘤标志物已得到认可并用于临床多年.在肝癌的诊断上,DCP与AFP之间无明显相关关系,并表现为一定的互补性,联合检测DCP与AFP有助于肝癌的早期诊断,同时对肝癌的疗效评价、预后评估有一定的指导意义.     

Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3

Current surveillance strategies for hepatocellular carcinoma (HCC) are applied uniformly in patients with cirrhosis, regardless of their cancer risk. The aim of this study was to compare the performance characteristics of the biomarkers alpha-fetoprotein (AFP), des-gamma carboxyprothrombin (DCP), and lectin-bound AFP (AFP-L3) in the diagnosis of HCC, and to determine the effect of risk factors for HCC on test performance. Eighty-four patients with HCC and 169 patients with cirrhosis were enrolled and their serum analyzed for total AFP, AFP-L3 and DCP. Receiver-operating characteristic (ROC) curves were constructed to determine the performance characteristics. DCP was significantly better than total AFP or AFP-L3 in differentiating HCC from cirrhosis, with a sensitivity of 86% and specificity of 93%. When subjects were divided into two groups by their risk for HCC, all 3 markers had a lower sensitivity and area under the ROC curve in the high-risk group compared to the low-risk group. In conclusion, DCP has the best performance characteristics of all 3 serum markers for the diagnosis of HCC. Serum biomarkers may be less sensitive and specific in the highest risk patients.     

Clinical application of determining serum AFP-IgM complexes for diagnosis of small hepatocellular carcinoma

Diagnosis of primary hepatocellular carcinoma (HCC) at early stages has obviously been improved since determination of serum levels of free alpha-fetoprotein (AFP) was implemented. AFP has been considered as the standard tumor marker of primary HCC, although certain patients have very low serum free AFP levels. In the present study, clinical application of measuring serum AFP-IgM immune complexes compared to the serum free AFP was evaluated for diagnosis of small HCC. One hundred and three healthy controls, 74 patients with primary HCC, 27 patients with liver cirrhosis and 63 patients with chronic hepatitis were included in the present study. Serum levels of AFP-IgM immune complexes and free AFP were determined by ELISA and electrochemiluminescence, respectively. The best cut-off values of AFP-IgM immune complexes and free AFP for the diagnosis of primary HCC were 300 AU/ml and 10 μg/l, respectively, according to the area under the curve (AUC). At these cut-off values, the sensitivities of AFP-IgM and AFP for HCC were 64.9% and 79.7%, respectively, with specificities of 75.6% and 80.3%, respectively. Combining positivity for both tumor markers, the specificity and accuracy of diagnosis of HCC were 89.1% and 79.0%, respectively. Moreover, when the diameter of the tumor was ≤ 3 cm (being considered as small HCC), the sensitivity and specificity were 100.0% and 75.3%, respectively. There was no significant correlation between AFP-IgM level, patient sex or age (p>0.05). The ROC area was significantly different between AFP-IgM and AFP (Z = 2.19, p = 0.0286). In addition, the serum AFP-IgM levels were significantly higher in the patients with tumor diameter ≤ 3 cm (1090.4 ± 571.8 AU/ml) than in the patients with tumor diameter >3 cm (604.9 ± 749.9 AU/ml). It is concluded that determining serum levels of both AFP-IgM immune complex and AFP may have potential benefit for the diagnosis of small HCC.