甲胎蛋白异质体检测在肝癌诊断中的意义

[目的]探讨联合检测血清甲胎蛋白(AFP)及甲胎蛋白异质体(AFP-L3)含量在肝癌诊断中的意义.[方法]采用全自动化学发光分析技术检测185例肝癌患者、225例肝良性病变患者以及 200名健康对照中血清AFP和AFP-L3的含量。[结果]肝癌组、肝脏良性病变组AFP、AFP-L3值均高于正常对照组(P＜0.05),肝癌组AFP和AFP-L3水平均高于肝脏良性病变组(P＜0.05).AFP诊断肝癌的灵敏度为68.11％,特异性为80.94％;而AFP-L3灵敏度为83.78%,特异性为96.00％;AFP及AFP-L3联合检测的灵敏度为93.51%,特异性为78.35%。[结论]AFP、AFP-L3联合检测对肝癌早期诊断及鉴别诊断具有一定意义.     

血清铁蛋白、甲胎蛋白和甲胎蛋白异质体联合检测对原发性肝癌诊断的临床意义

目的 探讨血清铁蛋白（Fer）、甲胎蛋白（AFP）、甲胎蛋白异质体（AFP-L3）联合检测对原发性肝癌的诊断价值.方法 健康对照组84名、原发性肝癌组92例、良性肝病组45例均同时检测血清Fer、AFP、AFP-L3.结果 原发性肝癌组血清Fer检测结果为（819.4±616.8）μg/L,AFP为（556.9±451.5）μg/L,AFP-L3为（109.0±62.5） μg/L,良性肝病组Fer检测结果为（229.3±155.5） μg/L,AFP为（6.0±4.2） μg/L,AFP-L3为（26.0±49.4） μg/L,健康对照组Fer检测结果为（125.6±110.5）μg/L,AFP为（2.8±0.8） μg/L,AFP-L3为（7.0± 1.8）μg/L,三者差异有统计学意义（均P＜0.01）.原发性肝癌组单独检测血清Fer的敏感度为85.9％,AFP的敏感度为71.0％,AFP-L3的敏感度为83.7％,联合检测Fer和AFP或AFP-L3可使检测敏感度提高到90.2％和95.7％,三者联合检测敏感度为98.9％.结论 联合检测血清Fer、AFP、AFP-L3三项指标可以提高原发性肝癌的诊断准确率.     

甲胎蛋白异质体浓度检测鉴别良恶性肝病的研究

 目的　探讨血清甲胎蛋白（AFP）异质体AFP-L3浓度检测在鉴别原发性肝癌与良性肝病中的临床价值。方法　选择180例AFP含量在400 ng／ml以下的肝病患者血清标本,应用酶联免疫吸附（ELISA）法检测AFP-L3浓度,分析原发性肝癌组与良性肝病组AFP-L3的浓度差异。结果　原发性肝癌组（102例）的AFP-L3浓度明显高于良性肝病组（78例）[（109.04±62.51）ng／ml比（25.96±49.43）ng／ml,t＝8.28,P＜0.001],以AFP-L3浓度38.0 ng／ml为临界值,原发性肝癌与良性肝病AFP-L3浓度异常的灵敏度为 82.35 %（84／102）,特异度为89.74 %（70／78）,诊断准确度为85.56 %（154／180）。结论　应用ELISA法检测AFP-L3在原发性肝癌与良性肝病的鉴别诊断中具有重要的临床应用价值。     

酶联免疫吸附法和凝集素微量离心柱法检测甲胎蛋白异质体的研究

目的:比较酶联免疫吸附法(enzyme linked immunosorbent,ELISA)和吸附柱微量离心柱法[lens cu-linaris agglutinin(LCA)-coupled spin column,ACSC]检测甲胎蛋白异质体(alpha-fetoprotein isoforms,AFP-L3)在甲胎蛋白(alpha-fetoprotein,AFP)阳性的良恶性肝病鉴别诊断中的价值。方法:采用ELISA法检测92例原发性肝癌(hepatocellular carcinoma,HCC),45例慢性肝炎及肝硬化患者血清中AFP-L3浓度,用ACSC法检测该批标本的AFP-L3/AFP%,比较两种方法对良恶性肝病鉴别诊断的价值。结果:ELISA法检测AFP-L3浓度和ACSC法检测AFP-L3/AFP%对92例原发性肝癌(HCC)的敏感性分别是83.69%和85.86%,对45例慢肝、肝硬化的特异性分别为88.88%和82.22%,ELISA法和ACSC法两种方法诊断原发性肝癌的符合率分别为85.40%和84.67%,在受试者工作特征曲线(recover operatin characteristic,ROC)下的面积AUC分别为0.819和0.823。结论:ELISA法检测AFP-L3浓度和ACSC法检测AFP-L3/AFP%在HCC鉴别诊断中具有相似的临床价值,但是ELISA法操作简便、省时、经济、患者易接受,更利于临床推广应用。     

甲胎蛋白异质体在肝癌早期诊断和预警作用研究

目的:探讨甲胎蛋白异质体(AFP-L3)在肝癌的早期诊断价值和对高危人群的预警作用。方法:分别用微量离心柱法和电化学发光法检测176例治疗前原发性肝癌患者和251例慢性肝病患者血清中的AFP-L3和AFP。并对其中的62例慢性肝病患者跟踪随访两年,动态监测AFP-L3。结果:肝癌组的AFP-L3敏感性和中位水平分别为84.09%和16.85,高于良性肝病组(P<0.05)。20相似文献   

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。     

GP73和AFP-L3联合检测在小肝癌诊断中的临床意义

目的:评价血清高尔基体蛋白73(GP73)和甲胎蛋白异质体3(AFP-L3)联合检测对低浓度甲胎蛋白(AFP)原发性小肝癌的诊断价值.方法:收集低浓度甲胎蛋白的小肝癌患者50例,非肝癌的消化系统疾病患者80例及健康对照者40例.用酶联免疫分析定量检测各组人群血清GP73含量,微量离心柱分离AFP-L3,罗氏电化学发光法测定总AFP和分离洗脱液中AFP-L3浓度,并计算AFP-L3占总AFP的比例(％).结果:各组血清GP73和AFP-L3水平比较,差异均有统计学意义(P均＜0.01),肝癌组阳性检出率均明显高于其他各组(P均＜0.01).GP73、AFP-L3和GP-73+ AFP-L3诊断小肝癌的灵敏度、特异性、准确率和曲线下面积分别为72.0％、93.3％、87.1％和0.820,62.0％、92.5％、83.5％和0.813,76.0％、96.7％、90.6％和0.870.结论:单独检测GP73和AFP-L3对低浓度AFP小肝癌的诊断价值较高,二者联合检测可提高诊断价值,用于AFP低浓度小肝癌的辅助诊断.     

血清巨噬细胞抑制因子1联合甲胎蛋白异质体3含量检测在原发性肝癌诊断中的价值

目的 探讨酶联免疫吸附（ELISA）法检测血清巨噬细胞抑制因子Ⅰ（MIC-1）联合甲胎蛋白异质体3（AFP-L3）对原发性肝癌的诊断价值.方法 选择116例临床确诊的原发性肝癌患者,应用ELISA法检测患者血清MIC-1和AFP-L3含量,分析二者联合检测在原发性肝癌诊断中的价值.结果 原发性肝癌组AFP-L3浓度为（127.12±51.43）ng/ml,明显高于正常对照组的（27.11±7.26） ng/ml（P＜ 0.001）,以AFP-L3＞ 38.0 ng/ml为临界值时,灵敏度为85.34％（99/116）,特异度为88.33％（53/60）,诊断准确度为86.36％（152/176）;原发性肝癌组MIC-1浓度为（3140.43±1138.23）pg/ml,明显高于正常对照组的（701.88±302.34） pg/ml（P＜0.001）,灵敏度为91.38％（106/116）,特异度为85.00％（51/60）,诊断准确度为89.20％（157/176）.二者联合检测灵敏度为83.62％（97/116）,特异度为91.67％（55/60）,诊断准确度为86.36％（152/176）.结论 MIC-1联合AFP-L3检测可提高原发性肝癌诊断的特异度,具有一定的临床价值.     

甲胎蛋白异质体3在肝细胞癌肝动脉化疗栓塞术疗效评价中的价值

目的探讨血清甲胎蛋白异质体3(AFP-L3)占甲胎蛋白(AFP)的比率在肝细胞癌(HCC)肝动脉化疗栓塞术(TACE)后疗效评价中的价值。方法用微量离心柱法分离AFP-L3,电化学发光法检测血清中AFP及AFP-L3的量,计算出AFP-L3占AFP的百分比,以AFP-L3≥10%为阳性判断标准。比较50例患者TACE前后AFP和AFP-L3的变化,结合复查时数字减影血管造影技术(DSA)和增强计算机断层扫描(CT)表现,分析AFP-L3在肝癌TACE疗效评价中的价值。结果根据实体瘤疗效评价标准(RECIST),分为完全缓解(CR)7例、部分缓解(PR)15例、稳定(SD)10例和疾病进展(PD)18例。50例患者术前AFP与术后AFP的差异无统计学意义(P>0.05),术前AFP-L3与术后AFP-L3的差异有统计学意义(P<0.01)。CR+PR+SD者术前AFP与术后AFP的差异有统计学意义(P<0.05),术前AFP-L3与术后AFP-L3的差异有统计学意义(P<0.01),AFP及AFP-L3下降百分率经配对样本比较的Wilcoxon符号秩检验,差异有统计学意义(P<0.01)。结论 AFP-L3是较AFP更准确的评价肝细胞癌TACE后疗效的肿瘤标志物。     

血清高尔基体蛋白73联合甲胎蛋白检测在原发性肝癌患者中的诊断价值

目的:探讨高尔基体蛋白73（golgiprotein 73,GP73）联合甲胎蛋白检测用于原发性肝癌诊断的临床意义。方法:收集2013年6 月至9 月天津医科大学肿瘤医院160 例血清,其中原发性肝癌患者46例,单纯肝硬化患者30例,其他消化系统肿瘤患者44例,健康者40例。应用酶联免疫吸附实验定量检测血清GP73水平,电化学发光免疫分析检测血清甲胎蛋白（alpha-fetoprotein ,AFP）水平。结果:GP73诊断原发性肝癌的敏感性达到73.9% ,与本研究中AFP 敏感性（56.5%）相比,前者有显著增高,差异有统计学意义（P<0.01）。 GP73和AFP 联合检测敏感性有显著提高,可以达到86.9% ,与单独一种相比敏感性有显著性差异（P<0.01）。 结论:GP73有可能作为原发性肝癌诊断的血清标志物之一,而GP73和AFP 的联合检测对原发性肝癌的诊断也有较好的应用价值。      

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.     

血清磷脂酰肌醇蛋白聚糖3在肝细胞癌中的表达及其与临床病理因素的相关性

目的 初步探讨肝细胞癌（HCC）患者血清和组织中磷脂酰肌醇蛋白聚糖3（GPC3）在HCC诊断中的临床应用价值.方法 采用酶联免疫吸附试验（ELISA）法和免疫组织化学染色法检测79例HCC患者血清和组织中GPC3表达水平,并与35例肝炎后肝硬化患者和30例健康体检者GPC3含量检测结果进行比较,采用Logistic回归模型对HCC患者GPC3表达水平与影响因素进行分析.结果 HCC组患者血清GPC3水平[（143.02±40.26） μg/L]明显高于肝硬化患者组[（6.15±4.31） μg/L]和健康对照组[（4.47±3.22）μg/L],三组间比较差异均有统计学意义（均P＜0.01）;GPC3阳性表达水平在HCC组织高于癌旁和远癌肝组织;GPC3蛋白表达与患者年龄、性别、肿瘤大小及甲胎蛋白（AFP）水平无明显相关性;与临床分期（x2 =4.250,P＜0.05）及肿瘤有无远处转移（x2=13.182,P＜ 0.001）关系密切.结论 GPC3检测对于HCC的诊断具有较好的特异性,联合血清AFP更有利于提高HCC诊断的敏感性,可作为HCC患者诊断及预后评估的标志物.     

Clinical significance of lens culinaris agglutinin-reactive fraction of serum alpha-fetoprotein in patients with hepatocellular carcinoma.

alpha-fetoprotein (AFP) is an important marker for the diagnosis of hepatocellular carcinoma (HCC) and has been widely used in clinical settings. Recently, the importance of lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) has been indicated. However, the clinical significance of the level of AFP-L3 protein in relation to the characteristics of HCC has not been fully evaluated. In the present study, both the ratio of AFP-L3 (AFP-L3%) and the absolute value of AFP-L3 (AFP-L3-AV) were examined in 80 patients with HCC, and evaluated with respect to characteristics of HCC such as grade of differentiation, size of tumor and morphological findings. Among HCC-specific tumor markers, AFP, AFP-L3% and protein induced in vitamin K absence (PIVKA-II), AFP showed the highest positive rate in patients with HCC, while AFP-L3% showed the lowest rate. AFP-L3% and AFP-L3-AV were, however, most significantly correlated with the grade of HCC differentiation, while AFP showed the least significant correlation. Furthermore, AFP-L3% was most significantly correlated with the size of HCC in patients with solitary HCC. Conversely, neither AFP-L3-AV nor PIVKA-II showed a significant correlation with the size of HCC. In relation to morphological differences of HCC, although AFP-L3%, AFP-L3-AV and PIVKA-II were significantly higher in the diffuse type of HCC than in the nodular type of HCC, AFP was most significantly correlated with the morphological differences of HCC. These results indicate that tumor markers for HCC, such as AFP, AFP-L3%, AFP-L3-AV and PIVKA-II, may play different roles in predicting the characteristics of HCC.     

联合检测AFP-L3％、GP73、GPC3在AFP低值原发性肝癌诊断中的价值

目的:本研究探讨血清甲胎蛋白异质体3百分含量(AFP-L3％)、高尔基蛋白73(GP73)、磷脂酰肌醇蛋白聚糖3(GPC3)联合检测在AFP低值原发性肝癌(primary hepatic carcinoma,PHC)诊断中的临床价值.方法:选取58例AFP低值原发性肝细胞癌患者(PHC组)、62例良性肝病患者(良性肝病组)和55例体检健康者纳入本研究.采用微量离心柱法分离AFP-L3,电化学发光法检测AFP与AFP-L3,计算AFP-L3％.依据试剂盒推荐以AFP-L3％≥10％作为阳性界值.采用酶联免疫吸附法检测GP73、GPC3血清浓度,其诊断PHC的cut-off值由受试者工作特征曲线(recover operation characteristic,ROC)确定.结果:PHC组AFP-L3％ (16.58％±5.12％)明显高于良性肝病组(9.16％±3.86％)和健康对照组(5.11％ ±2.03％,P＜0.001);PHC组GP73浓度(167.83±69.56) ng/ml明显高于良性肝病组(59.43±28.37) ng/ml和健康对照组(10.39±4.22) ng/ml,P＜0.001;PHC组GPC3浓度(116.52±48.21) μg/L明显高于良性肝病组(28.43±11.25)μg/L和健康对照组(3.25±1.46) μg/L,P＜0.001.以AFP-L3％≥10％作为阳性界值诊断PHC,诊断灵敏度为82.76％,特异度为82.05％,诊断正确率为82.28％;依据ROC曲线,GP73诊断PHC的cut-off值为81.86 ng/ml,诊断灵敏度为77.59％,特异度为82.91％,诊断正确率为81.14％;依据ROC曲线,GPC3诊断PHC的cut-off浓度为35.43μg/L,诊断灵敏度为70.69％,特异度为77.78％,诊断正确率为75.43％;联合检测AFP-L3％、GP73、GPC3水平诊断PHC的灵敏度为87.93％,特异度为84.62％,诊断正确率为85.71％.结论:肿瘤标志物AFP-L3％、GP73、GPC3可作为早期诊断和鉴别诊断PHC的良好指标,联合检测可显著提高诊断正确率.     

Clinicopathological significance of carbonic anhydrase 9, glucose transporter-1, Ki-67 and p53 expression in oral squamous cell carcinoma

The fucosylated fraction of α-fetoprotein (AFP-L3) is a specific marker for hepatocellular carcinoma (HCC). However, conventional AFP-L3% (c-AFP-L3%) has not always been reliable in cases with low serum α-fetoprotein (AFP) levels. In this study, we evaluated the clinical utility of a newly developed assay, highly sensitive AFP-L3% (hs-AFP-L3%). Subjects included 74 patients with benign liver disease (BLD), including chronic hepatitis and cirrhosis, and 94 with HCC. Serum hs-AFP-L3% was significantly higher than c-AFP-L3% in patients with early-stage HCC (solitary or <20 mm in diameter). Additionally, hs-AFP-L3% was significantly increased in patients with well-differentiated HCC. In patients with serum AFP <20 ng/ml, the sensitivities of c-AFP-L3% and hs-AFP-L3% were 12.5 and 44.6%, respectively, at a cut-off value of 5%. In 59 BLD patients with serum AFP <20 ng/ml, the HCC-positive rate in patients with hs-AFP-L3% ≥ 5% was significantly higher compared to those with hs-AFP-L3% <5% during the follow-up period (median, 35 months; range, 5-48 months). Importantly, none of the BLD patients with both serum AFP <20 ng/ml and hs-AFP-L3% <5% developed HCC. These results indicated that hs-AFP-L3% is useful for early detection of HCC in BLD patients, even for those with serum AFP <20 ng/ml. Furthermore, since hs-AFP-L3% increases before HCC is detectable by various advanced imaging modalities, this assay may help identify BLD patients with a higher risk of HCC.     

Clinical utility of highly sensitive Lens culinaris agglutinin-reactive alpha-fetoprotein in hepatocellular carcinoma patients with alpha-fetoprotein <20 ng/mL

The Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) has been used as a diagnostic and prognostic marker of hepatocellular carcinoma (HCC). The analytical sensitivity of a conventional method for AFP-L3% is not sufficient in patients with a low AFP level. This study was performed to determine the clinical utility of a newly developed highly sensitive AFP-L3% (hs-AFP-L3%) assay in patients with an AFP level <20 ng/mL. In the cohort study, serum samples obtained from 270 patients with newly diagnosed HCC before treatment and 396 patients with chronic liver disease at Ogaki Municipal Hospital, in both of which the AFP level was <20 ng/mL, were measured for conventional AFP-L3% (c-AFP-L3%), hs-AFP-L3% and des-gamma-carboxy prothrombin (DCP). Diagnostic sensitivity and specificity of hs-AFP-L3% at a cut-off level of 5% were 41.5% and 85.1%, respectively, significantly increasing the sensitivity from 7.0% for c-AFP-L3%. Multivariate analysis identified hs-AFP-L3% as an independent factor associated with reduced long-term survival. The survival rate of patients with high hs-AFP-L3% (≥ 5%) before treatment was significantly poorer than that of patients with low hs-AFP-L3% (<5%) (P < 0.001). In patients with AFP <20 ng/mL, measurements of AFP-L3% by the highly sensitive method before treatment were more useful for diagnosis and prognosis of HCC than by the conventional method.