The usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of alpha-fetoprotein in the differential diagnosis of neoplastic diseases of the liver.

The degrees of glucosaminylation (glucosaminylation index) and fucosylation (fucosylation index) of alpha-fetoprotein (AFP) were determined in serum samples of 351 patients with hepatocellular carcinoma (HCC), 47 with carcinoma metastatic to the liver from digestive organs, five with mixed cholangiocellular and HCC, and 176 with benign liver diseases. The glucosaminylation index of AFP in patients with carcinoma metastatic to the liver (42 +/- 23%, mean +/- SD) was significantly higher than that in patients with HCC (5 +/- 7%, P less than 0.001) or that in patients with benign liver diseases (2 +/- 4%, P less than 0.001). The fucosylation indices of AFP in patients with carcinoma metastatic to the liver, with HCC, and with benign liver diseases were 76 +/- 25%, 42 +/- 30%, and 4 +/- 6%, respectively. Thus, the fucosylation indices of AFP were high in two neoplastic liver diseases (carcinoma metastatic to the liver and HCC) and low in benign liver diseases, whereas the glucosaminylation indices were high in carcinoma metastatic to the liver but low in HCC and benign liver diseases. When the values of 30% and 80% were used as the level of the glucosaminylation and fucosylation indices, respectively, to discriminate carcinoma metastatic to the liver from HCC, 40 of 47 patients with carcinoma metastatic to the liver (85%) were able to be discriminated from HCC (sensitivity). The specificity, the positive predictive value, and the overall accuracy were 86% (302/351), 45% (40/40 + 47 + 3 - 2) and 86% (40 + 302/47 + 351), respectively. These data suggest that the combined information in these two indices provides a potent criterion for the diagnosis of neoplastic diseases of the liver.     

Value of serum alpha-fetoprotein and ferritin in the diagnosis of hepatocellular carcinoma

Alpha-fetoprotein (AFP) and ferritin in the serum were determined by radioimmunoassay and enzyme immunoassay, respectively, in 224 healthy subjects, 55 patients with benign hepatic disease and 44 patients with hepatocellular carcinoma (HCC). The AFP levels in the serum were significantly higher in patients with HCC than in healthy subjects and in patients with benign hepatic disease, but this level was not a satisfactory indicator of small HCC since it was elevated in only 75.0% of the patients with a tumor of less than 3.0 cm in its greatest diameter. Although serum ferritin was elevated in only 56.8% of the patients with HCC, the combination of these two tests raised the diagnostic rate of HCC from 65.9% by serum AFP measurement alone to 88.6% with no appreciable decrease in the specificity for HCC. In particular, it raised the diagnostic rates of lesions of less than 3.0 cm in the greatest diameter from 75.0% by measuring AFP alone to 100%. Thus the combination of AFP and ferritin measurement in the serum is useful for the early detection of HCC.     

Clinical Value of Hepatoma-Specific Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide and the number 2 cause of cancer mortality in Chi- na.[1] It often develops in cases of liver cirrhosis and chronic hepati- tis. [1-3] Advanced imaging procedures including utrasonograph…     

The ratio of fucosylation of alpha-fetoprotein in hepatoblastoma

Hepatoblastoma differs from the adult type of hepatoma in clinical and pathologic features. The ratio of fucosylation of serum alpha-fetoprotein (AFP) was determined in seven patients with hepatoblastoma and in 21 infants and children with otherwise elevated serum AFP, using the improved technique of lentil agglutinin-affinity immunoelectrophoresis. The clinical data for the seven patients with hepatoblastoma were also reviewed. The ratio of fucosylation of AFP was significantly higher in all seven patients with hepatoblastoma, whereas it was minimal in all other cases of benign hepatic conditions such as neonatal hepatitis or biliary atresia, as well as in normal newborns. The ratio of fucosylation in hepatoblastoma, however, definitely decreased with the age of the patient at presentation. This finding suggests a correlation between fucosylation and a rapid rate of tumor growth, because all hepatoblastomas are believed to originate early in fetal life.     

THE USEFULNESS OF ~(99)Tc-PMT DELAYED HEPATOBILIARY IMAGING IN THE DIAGNOSIS OF SMALL HEPATOCELLULAR CARCINOMA

This investigation was aimed to assess the usefulness of delayed hepalobillary Imaging in the diagnosis of small hepatocellular carcinoma (HCC). Sixty-two patients with this hepatic cancer were Included in the study. 56 males and 6 females, with a mean age of 50. 6 yr. (32 - 72 years old). All patients were performed by surgery, verified histologically, and these tumors were smaller than 5 cm. Liver scans were performed 5 minutes, 2 hours and 5 hours after the administration of radlopharmaceutices. In 31 of the 62 patients (50%), the tumor exhibited equal radioactivity uptake or greater radioactivity uptake than the surrounding liver in delayed imaging. And the sensitivity was 33. 3% (2/6), 41.2% (7/17), 60.0% (9/15) and 54.2% (13/24) In the tumor size was ≤2 cm, 2-3cm, 3-4 cm and 4 - 5 cm, respectively. The smallest mass to be detected was only 1. 2 cm. The uptake of radiopharmaceutic was nonsignificantly related to serum AFP level and hepatic cirrhosis (P>0. 05). These results show that 99-Tc-PMT del     

Early diagnosis of hepatocellular carcinoma with lectin electrophoresis of serum alpha-fetoprotein

A sensitive procedure involving lectin affinity electrophoresis of alpha-fetoprotein (AFP) was established. AFPs electrophoresed on lectin-containing gels were blotted on nitrocellulose membrane which was precoated with the specific antibody to AFP and stained with peroxidase-labeled anti-AFP antibody. This method could detect as little as 4 micrograms/l of purified AFP dissolved in buffer, or 50 micrograms/l in serum specimens. A number of patients with liver disease have been followed for long periods in Nihon University Hospital, Tokyo. Serum specimens were collected serially and stored frozen. We have reinvestigated retrospectively 6 series of serum specimens by the lectin-immunoblotting technique and found 3 cases that revealed a hepatocellular carcinoma-specific AFP variant at a very early stage, in advance of any other evidence of hepatocellular carcinoma by clinical examination.     

Controversies in surveillance and early diagnosis of hepatocellular carcinoma

The surveillance of hepatocellular carcinoma (HCC) is an established approach to detect early cancers in patients with defined risks. However, there are still varied controversies and issues to be addressed regarding the optimal surveillance methods and interval. Moreover, there are discrepancies in the opinion or practice of HCC surveillance between Eastern and Western countries. The Western strategy of ultrasound without a biomarker such as α-fetoprotein reflects the cost-effective utilization of limited resources. On the contrary, combined measurements of biomarkers in Eastern countries are based on the assumption that increased detection of early cancers could result in an overall survival benefit. To address this complicated issue, a prospective study comparing different surveillance tests might be required. More importantly, discovery of a novel biomarker with higher performance would be an alternative.     

肝细胞癌中miR-122的表达及其与血清AFP水平的关系

目的 探讨miR-122在肝细胞癌（肝癌）中的表达水平及其与血清AFP水平的关系。方法 用荧光定量PCR分别检测78例肝癌患者肝癌组织中miR-122的表达水平,电化学发光免疫分析法检测肝癌患者术前血清AFP水平,分析miR-122表达与血清AFP水平的关系。结果78例肝癌患者肿瘤组织miR-122的相对表达量为（23.71±13.33）％,其中高、中分化组织为（26.90±13.64）％,明显高于低分化者的（16.54±9.40）％（P=0.001）。78例肝癌患者血清AFP平均值为（741±382）ng／ml。miR-122表达与性别、年龄、淋巴结转移、肿瘤大小、血管浸润、分期等无关,miR-122在肝癌和癌旁组织中的表达与血清AFP水平呈负相关（r=-0.863,P＜0.01）。结论 miR-122表达与血清AFP水平呈负相关,在低分化肝癌中表达更低,提示miR-122是肝癌的一个潜在预后因子。     

联合检测血清miR-125b和AFP对原发性肝细胞癌的诊断价值

  目的   探讨血清中miR-125b作为原发性肝细胞癌（hepatocellular carcinoma,HCC）的血清标志物的可能性和联合检测miR-125b和AFP对HCC的诊断价值。   方法   通过实时荧光定量PCR（quantitative real-time polymerase chain reaction,RT-qPCR）检测65例HCC患者和30例健康对照组的血清miR-125b表达量,分析其对HCC的诊断价值,以及与HCC临床病理资料参数间的关系。   结果   HCC患者组血清miR-125b表达与对照组相比较低,且两者的差异有统计学意义（P < 0.05）。miR-125b的表达与患者性别、年龄、乙肝表面抗原阳性、AFP、ALT和α-GGT的表达水平无关（P > 0.05）。miR-125b的表达与患者肝硬化、肿瘤大小和TNM分期有关,且差异有统计学意义（P < 0.05）。单独检测miR-125b的ROC曲线下的AUC为0.917（95%CI:0.851~0.960,P < 0.001）,灵敏性为85.9%,特异性为93.5%,联合miR-125b和AFP检测的ROC曲线下的AUC为0.951（95%CI:0.894~0.982,P < 0.001）,灵敏性为92.9%,特异性为93.5%,检测AFP < 20 μg/L的HCC患者血清miR-125b的ROC曲线下的AUC为0.889（95%CI:0.776~0.957,P < 0.001）,灵敏性为84.0%,特异性为87.1%。   结论   联合检测血清miR-125b和AFP对早期诊断原发性HCC具有重要的临床价值。      

肝癌早期诊断标志物

肝癌(HCC)的早期诊断对其预后非常关键,筛选出能够帮助肝癌早期诊断的肿瘤标志物成为迫切需要.研究表明包括人宫颈癌基因、γ-谷氨酰转移酶mRNA、人端粒酶反转录酶mRNA、磷脂酰肌醇蛋白聚糖-3、高尔基体蛋白73、血管内皮生长因子、转化生长因子β1等在内的一些基因及转录产物和蛋白质可以作为肝癌早期诊断的标志物.     

甲胎蛋白抗肝细胞癌研究进展

甲胎蛋白(AFP)在肝细胞癌(HCC)组织特异高效表达.将外源治疗基因(如自杀基因、免疫基因等)置于AFP启动子/增强子下游,构建靶向特异性转录载体,靶向基因治疗HCC.AFP基因编码的抗原表位多肽可激活人体细胞免疫机制,诱导特异性CTL产生,杀伤HCC细胞.因此AFP完全有可能被利用作为HCC免疫及基因治疗的有效靶向途径.     

The significance of early alpha-fetoprotein level changes in predicting clinical and survival benefits in advanced hepatocellular carcinoma patients receiving sorafenib

Background.

The role of serum alpha-fetoprotein (AFP) changes in predicting the treatment outcomes of advanced hepatocellular carcinoma (HCC) patients to sorafenib remains unknown.

Methods.

Serum AFP was collected prospectively at baseline and subsequent follow-up visits in parallel with clinical and survival outcomes. AFP response was defined as a relative drop of AFP >20% of the baseline level after 6 weeks of sorafenib. The relationship between AFP response and the treatment outcomes was first explored in patients who received sorafenib in a phase II study. Subsequently, an independent validation set of patients were obtained to validate the association of AFP response to clinical outcomes.

Results.

Included in the exploration and validation sets for analysis were 41 and 53 patients, respectively, with baseline AFP level >20 μg/L. In the exploration cohort, AFP response was significantly associated with clinical benefit (CB) rate (relative chance 3.4, 95% confidence interval [CI], 1.1–11.1), and multivariate analysis indicated that AFP response was associated with significantly better progression-free survival (PFS) (hazard ratio [HR], 0.31; 95% CI, 0.13–0.76) and marginally better overall survival (OS) (HR, 0.30; 95% CI, 0.09–1.02). When applying AFP changes in the validation set, significant associations were again found between AFP response with CB rate (relative chance, 5.5; 95% CI, 2.3–13.6) and PFS (HR, 0.12; 95% CI, 0.04–0.30) but not OS (HR, 0.61; 95% CI, 0.27–1.26).

Conclusion.

Drop in AFP level at 6 weeks is an exploratory early surrogate for both CB and PFS in advanced HCC patients receiving sorafenib.     

A simultaneous monitoring of Lens culinaris agglutinin A-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin as an early diagnosis of hepatocellular carcinoma in the follow-up of cirrhotic patients

To elucidate the risk factors for developing hepatocellular carcinoma (HCC) during the follow-up of patients with liver cirrhosis (LC), outpatients with LC were examined periodically by means of serum biochemical assessments, ultrasonography, and computed tomography. Risk factors for HCC were statistically analyzed. We also examined an efficacy of Lens culinaris agglutinin A-reactive profiles of alpha-fetoprotein (AFP-L3%) and des-gamma-carboxy prothrombin (DCP) value using a highly sensitive DCP determination kit (ED036) for the early recognition of HCC. The AFP-L3% and the ED036 value were retrospectively determined with stored serum samples. HCC was diagnosed in 21 of the 78 patients with LC during the follow-up period (mean follow-up period: 42 months). The estimated cumulative incidence of HCC was 25% with 3 years and 48% with 5 years. The most significant risk factor for the development of HCC in LC patients was found to be the mean serum AFP concentration from the year before the HCC detection (p=0.02). At the time of the recognition of HCC, the positive rates of the tumor markers were: serum AFP concentration 14%, serum DCP value 5%, AFP-L3% was 33%, and that of ED036 43%. The positive rate in collaborative use of AFP-L3% and ED036 was 67%. The simultaneous determination of the AFP-L3% and the ED036 value was shown to be effective for the early detection of HCC.     

Serum alpha-fetoprotein and variant alkaline phosphatase in human hepatocellular carcinoma

Alpha-fetoprotein and variant alkaline phosphatase were studied in a group of patients with hepatoma. The incidence of positive alpha-fetoprotein was 67.6% in confirmed cases. Variant alkaline phosphatase was present only in patients with positive fetoprotein test, and it appeared in only 28.6% of the cases.     

肝超声造影监测和早期诊断微小肝癌的应用价值

背景与目的：我国肝癌发病率高,原发性肝癌常在肝硬化的基础上发生,早期诊断较为困难。本研究应用实时超声造影对肝癌高危患者进行定期跟踪监测,探讨其早期发现和诊断微小肝癌的临床应用价值。方法：2011年2月-2013年11月针对320例肝癌高危患者进行定期的肝常规超声检查和追踪定位的肝超声造影检查,根据肝内病灶在超声造影不同时相的增强表现特点鉴别诊断其良恶性。结果：320例肝癌高危患者定期随访中,经肝超声造影发现和诊断微小肝细胞癌20例,并经手术病理证实,包括直径≤1.0 cm肝癌7例、1.1~2.0 cm肝癌13例。其中6例(30.0%)呈不典型的“快进同出”型表现;病灶小,灰阶超声上呈等回声是超声造影表现不典型的主要因素。结论：常规超声和超声造影对肝癌高危患者的定期跟踪监测,可早期发现微小肝癌,使患者得到及时治疗。     

Altered glycosylation of alpha-fetoprotein in hepadnavirus-induced hepatocellular carcinoma of the woodchuck.

Altered glycosylation of alpha-fetoprotein (AFP) has been proposed as a marker of hepatocellular carcinoma (HCC) in humans. The lectin-binding properties of woodchuck AFP were investigated to determine if woodchuck hepatitis virus (WHV)-induced HCCs are also accompanied by changes in AFP glycosylation. Ninety-eight to 100% of the AFP from normal, WHV-free woodchucks with physiologic AFP elevations and from WHV-carrier woodchucks with HCC bound to concanavalin A, indicating that virtually all of the AFP was glycosylated. Three percent or less of the serum AFP of normal woodchucks bound to Lens culinaris agglutinin (LCA). In contrast, the AFP from woodchucks with HCC had an increased LCA-binding fraction (range, 8-77%). The increased LCA-binding AFP in WHV-induced HCC is analogous to that which frequently accompanies hepatitis B virus (HBV)-induced HCC in humans. This study corroborates the relationship of altered glycoconjugate synthesis to virus-induced malignant transformation, confirms the importance of AFP glycoforms as markers of HCC, and demonstrates that the WHV-infected woodchuck should be useful in investigating changes in AFP glycosylation during hepadnavirus hepatocarcinogenesis and HCC growth.