血清TSGF,AFP,GGT检测对肝癌诊断的意义

肝癌患者早期很少临床表现,难于发现,恶性程度高易转移,死亡率高。目前检测肝癌的方法较少,放射免疫法检测血清中的甲胎蛋白(AFP)的含量。特异性高,阳性率达80 %左右,有少部份不产生AFP的肝癌病人则AFP阴性,使患者失去了及时的治疗机会。我们用组合方式检测血清中恶性肿瘤相关物质(TSGF)、AFP、γ-谷氨酰基转移酶(GGT)的含量对提高肝癌诊断的敏感性和特异性有较大的价值,对肝癌的早期诊断十分必要。现将结果报告如下。1　对象和方法1 1　对象　患者组为本院住院肝癌患者10 0例(男78,女2 2 ) ,年龄(4 5～70 )岁,肝硬化患者10 0例(男6…     

磷脂酰肌醇蛋白聚糖3基因与肝癌关系的研究进展

原发性肝癌(PHC)是目前世界上最常见的恶性肿瘤之一.肝癌的发生是由化学致癌物、病毒、遗传等多病因作用引起的.其恶性程度高,预后差,进展较快.早期诊断、治疗对肝癌患者的预后至关重要,目前临床诊断主要依靠影像学检查及肿瘤标志物甲胎蛋白(AFP).但AFP的敏感性和特异性均不高.近年来,一种新的肝癌肿瘤学标志物磷脂酰肌醇蛋白聚糖3(GPC3)成为不少国内外学者研究热点,其在肝癌中无论mRNA水平还是蛋白质水平均为高表达,GPC3对PHC的诊断具有较高的敏感性和特异性,其在AFP阴性的肝癌中亦有表达.     

简单、快速同时检测乙肝表面抗原和甲胎蛋白胶体金免疫层析方法的建立

检测乙肝表面抗原 (HBsAg)和甲胎蛋白 (AFP)是诊断乙型肝炎病毒感染和辅助诊断原发性肝癌的两个重要的实验室指标。我国某些地区的肝癌 90 %是从肝硬化发展而来 ,每年有 3%～ 7%的肝硬化病人发展为肝癌。AFP大于 4 0 0 μg L的患者多数伴有乙型肝炎 ,说明乙肝病毒与AFP升高关系较密切〔1〕。AFP对肝癌的早期辅助诊断价值已被公认。而检测AFP对判断慢性肝炎病人是否继发原发性肝癌有帮助。因此在临床上 ,对于许多被怀疑患乙型肝炎病毒感染或原发性肝癌的病人 ,常常需要同时测定其HBsAg和AFP。在我国 ,肝癌的人群普查均同时测定HBs…     

联合检测血清中ADA,AFU,AFP,CEA在提高临床诊断原发性肝癌时的价值

目的：原发性肝癌是我国常见的恶性肿瘤之一,治疗困难,预后较差,死亡率极高。因此原发性肝癌早期诊断及早期治疗,尤其显得重要。本文主要探讨血清中a-L-岩藻糖苷酶(AFU)、腺苷脱氨酶(ADA)、甲胎蛋白(AFP)及癌胚抗原(CEA)联合检测对原发性肝癌诊断的指导作用。方法分别采用电化学发光免疫法及化学速率比色法,设正常健康对照组78例,原发性肝癌组64例,均同时检测血清AFU、ADA、AFP、CEA。结果原发性肝癌组血清ADA、AFU、AFP、CEA单独检测时的敏感性分别为72.0%、78.0%、81.2%和41.0%,联合检测AFP和AFU或CEA可使检测敏感性提高到87.0%和77.0%,四者联合检测敏感性为93.8%。结论联合检测ADA、AFU、AFP、CEA在肝癌患者血清中含量明显增高,在原发性肝癌发生、发展中具有重要作用,大大提高原发性肝癌的诊断率。     

原发性肝癌患者α-L岩藻糖苷酶(AFU)及AFP联检的临床应用

原发性肝细胞癌(HCC)是我国常见的恶性肿瘤之一,由于早期缺乏典型的临床表现,很难诊断,甲胎蛋白(AFP)作为诊断原发性肝癌的首选肿瘤标志物,但仍有2 0 4 0 %的原发性肝癌患者AFP呈阴性[1 ] ,我们通过联合检测的方法同时开展了AFP的含量及α-L岩藻糖苷酶(AFU)活性检测,观察是否可     

甲胎蛋白异质体L3预警原发性肝癌的研究

目的 探讨甲胎蛋白异质体(AFP-L3)的检测在预警原发性肝癌中的作用.方法 对100例AFP升高肝病患者血清,应用甲胎异质体微量离心柱分离并洗脱获得AFP-L3,再同时检测原始血清中的AFP以及AFP-L3含量,计算AFP-L3在AFP中的比例,对AFP-L3异常升高者、正常者进行跟踪,结合6个月后临床诊断结果 ,分析AFP-L3升高在鉴别良性肝脏病变与预警肝癌中的作用.结果 肝癌、疑似肝癌患者与良性肝病患者中的AFP-L3阳性率差异有统计学意义(分别为81.80%、73.68%、11.80%,P＜0.05).未确诊肝癌(疑似HCC、肝病)的患者中,AFP-L3阳性的21例中有12例在6个月内被诊断为HCC,而且有6例是通过B超、CT等影像学手段被早期确诊的单发性小肝癌.AFP-L3阴性的62例标本中,6个月内有3例发生肝癌,AFP-L3阳性发生肝癌的危险率增加了11.9倍.结论 AFP-L3与AFP值无相关性,可以作为一个独立肝细胞癌诊断因子.AFP-L3的测定对于AFP升高时良、恶性肝病的鉴别及肝癌的早期预警诊断具有重要意义.     

AFP与PIVKA-Ⅱ联合检测在原发性肝癌诊断中的应用研究

目的 探究甲胎蛋白AFP与异常凝血酶原PIVKA-Ⅱ对原发性肝癌的诊断价值.方法 回顾性研究首都医科大学附属北京佑安医院2016年1月至3月收治的肝病患者268例,其中病毒性肝炎患者59例、肝硬化患者96例、其他肝病患者33例和原发性肝癌患者80例(早期50例、晚期30例),对其AFP和PIVKA-Ⅱ的检测结果进行统计分析.结果 原发性肝癌组血清AFP和PIVKA-Ⅱ水平明显高于其他疾病组(P ＜0.005);AFP和PIVKA-Ⅱ的ROC曲线下面积分别为0.854和0.926,两指标联合诊断原发性肝癌的ROC曲线下面积为0.951;血清AFP单独诊断原发性肝癌的敏感性和特异性分别为87.50％和66.49％,PIVKA-Ⅱ单独诊断原发性肝癌的敏感性和特异性分别为90.00％和85.11％.联合检测对原发性肝癌的诊断效率,并联联检可将敏感性提高到97.50％;串联联测可将特异性提高到94.15％;经相关性分析发现,在早期原发性肝癌的诊断上两指标Spearman相关系数为0.044(P =0.763),两者无相关性.结论 血清PIVKA-Ⅱ用于诊断原发性肝癌有较高的敏感性和特异性,其诊断价值高于AFP;两指标在早期原发性肝癌的诊断上没有相关性,两指标联合可以明显提高早期原发性肝癌的诊断效率.     

三种肿瘤标志物联合铁蛋白检测对原发性肝癌的诊断价值分析

目的探讨血清甲胎蛋白(AFP)、糖类抗原199(CA199)和癌胚抗原(CEA)联合铁蛋白(FER)检测对原发性肝癌的诊断价值。方法选取2016年1月至2017年1月我院收治的63例原发性肝癌患者作为观察组,另外选取同时期的63例正常健康体检者作为对照组,比较两组研究者AFP、CA199、CEA、FER水平,并计算不同检查指标对原发性肝癌诊断灵敏度及特异度。结果观察组患者AFP、CA199、CEA、FER水平明显高于对照组,差异具有统计学意义(P0.05);AFP+CA199+CEA检测诊断原发性肝癌诊断灵敏度及特异度分别为80.95%、84.12%,AFP+CA199+CEA+FER检测诊断原发性肝癌诊断灵敏度及特异度分别为96.82%、98.41%,明显高于AFP+CA199+CEA检测,差异具有统计学意义(P0.05)。结论 AFP、CA199、CEA联合FER检测诊断原发性肝癌灵敏度及特异度高,值得临床推广。     

AFP、CA125、SF在肝癌诊断中的联合应用

正原发性肝癌是我国常见的消化系统恶性肿瘤之一,死亡率高。实验室诊断肝癌最常见也是最灵敏的肿瘤标记物是血清甲胎蛋白(AFP)的检测,但仍有部分患者AFP阴性。CA125是目前妇科最常检测的肿瘤标志物之一,尤其是对卵巢癌有重要的辅助诊断价值。本文采用血清测定AFP、CA125、铁蛋白(SF),探讨其联合检测在肝癌诊断中的临床应用价值。     

用RIA法测定高浓度AFP时几种稀释液的比较

甲胎蛋白(AFP)对原发性肝癌(PHC)的早期诊断，确立诊断和疗效观察具有重要价值，血清AFP浓度对PHC的早期诊断，特别是手术效果和预后的观察，化疗效果的评价等具有非常重要的意义。在AFP的稀释检测过程中，稀释液的选择是影响测定结果的重要因素。本文对几种稀释液进行了比较试验，结果报告如下。     

Significance of serum microRNA-21 in diagnosis of hepatocellular carcinoma (HCC): clinical analyses of patients and an HCC rat model

MicroRNAs (miRNAs) are associated with human carcinogenesis and tumor development. Moreover, serum miRNAs can reflect the level of tissue miRNAs and be potential tumor markers. Serum microRNA-21 (miR-21) is overexpressed in many human cancers including hepatocellular carcinoma (HCC). However, how serum miR-21 changes during the HCC formation and whether miR-21 plays a regulatory role in this whole process are unknown. The current study evaluated the prognostic and diagnostic potential of serum miR-21 in HCC patients. Next, we established a HCC rat model and collected the blood and liver tissues at regular time points. AFP from the serum, RNA from the serum and liver tissues were collected and quantified separately. The results revealed that tissue and serum miR-21 was upregulated significantly in the groups of cirrhosis, early and advanced HCC compared with normal and fibrosis groups. The AFP levels were increased in early and advanced HCC compared with other groups. Then, the changes of miR-21 downstream proteins (i.e., programmed cell death 4 [PDCD4] and phosphatase and tensin homolog [PTEN]) in the liver tissues were measured. PDCD4 and PTEN expression was decreased gradually after tumor induction and negatively correlated with miR-21 expression. All these results suggested that serum miR-21 was associated with the prognosis of HCC; the changes in serum miR-21 were earlier and more accurately reflected the pathogenesis of HCC than AFP; therefore, it could be used as an early diagnostic marker for HCC. Our in vivo experiments further confirmed that miR-21 plays an important role in promoting the occurrence and development of HCC by regulating PDCD4 and PTEN.     

GP73 expression and its significance in the diagnosis of hepatocellular carcinoma: a review

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and its incidence has been increasing worldwide. Serum alpha-fetoprotein (AFP) levels and abdominal ultrasound have been widely used for diagnosis as well as surveillance of HCC. However, the sensitivity and specificity of both AFP levels and ultrasound for HCC surveillance have some shortcomings, particularly in the early stages of the disease. Golgi protein-73 (GP73) is a type II Golgi-localized integral membrane protein that is normally expressed in epithelial cells of many human tissues. It is essential for human survival, and might have multiple roles for GP73 in epithelial cell function such as in the kidney and liver. However, details of its biochemical function and regulation of GP73 expression are unknown at present. GP73 expression is upregulated in serum samples from patients with liver disease, with expression being highest in HCC. Therefore, it may be useful as a new serum marker for detection of HCC in at high-risk population. But, this hypothesis needs to be proven in large cohorts.     

Serum alpha-fetoprotein and its lectin reactivity in liver diseases: a review.

Increased serum concentration of alpha-fetoprotein (AFP) can be found in benign and malignant liver diseases, in yolk sac tumors, and in several nonhepatic neoplasms at advanced stage. The frequency and level of elevated serum AFP are highest in hepatocellular carcinoma (HCC) and yolk sac tumors. Most levels of serum AFP in HCC are greater than 500 ng per mL, whereas the serum AFP in most of the benign liver diseases is only moderately elevated and is transient in nature. Determination of lectin reactivity of serum AFP is helpful for the differentiation of HCC from other diseases associated with elevated serum AFP. Determination of Len culinaris agglutinin (LCA) reactivity of serum AFP is useful for the differentiation of HCC from benign liver diseases, and for early detection of hepatoma. Determination of concanavalin A (Con A) nonreactive AFP variant is useful for the differentiation of HCC from yolk sac tumors and may also allow for the differentiation of HCC from nonhepatic neoplasms. However, reaction with several lectins may be required if differentiation among various nonhepatic neoplasms is needed.     

AFP-L3在肝细胞癌早期诊断和疗效监测中的价值

为了探讨甲胎蛋白异质体(AFP-L3)在肝细胞癌的早期诊断和疗效监测价值,本研究联合应用微量离心柱法和电化学发光法随访监测83例原发性肝细胞癌患者和57例首诊为非肿瘤性慢性肝病患者血清中的AFP和AFP-L3水平。原发性肝细胞癌患者监测时间为肝癌术前至术后6个月,慢性肝病患者监测时间为首诊前至诊后2年。同时收集原发性肝细胞癌患者门脉癌栓情况、肿瘤分化程度、临床分期、肿块大小等临床诊断指标。研究结果为,随访的22例AFP-L3持续阳性的慢性肝病患者平均3.15个月均确诊为肝癌,肝癌发生率为45.45%;4例AFP-L3阴性变阳性的慢性肝病患者,平均8.17个月均确诊为肝癌,肝癌发生率为100%;31例AFP-L3持续阴性的慢性肝病患者,平均11.75个月确诊为肝癌,肝癌发生率为9.68%。各组相比差异有统计学意义。原发性肝细胞癌患者手术有效者AFP和AFP-L3水平明显下降,而病情稳定和进展者二者水平无显著变化或升高。AFP-L3水平与肿瘤分化程度相关,而与门脉瘤栓、临床分期和肿块大小不相关。在有门脉瘤栓组、低分化肝癌组、Ⅰ期肝癌组和小肝癌组中,其AFP-L3的阳性率分别为81.97%、100%、75%和77.78%。由此可知AFP-L3在肝细胞癌早期诊断和疗效监测中具有重要的临床价值。     

Combined analysis of AFP and HCCR-1 as an useful serological marker for small hepatocellular carcinoma: a prospective cohort study

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world. The only serological marker widely used for the diagnosis of HCC is alpha-fetoprotein (AFP). Despite that AFP is widely used for the diagnosis of HCC, it has a limit as a serological marker due to its low sensitivity and specificity. The human cervical cancer proto-oncogene 1 (HCCR-1) was previously reported as a new biomarker for HCC. To further evaluate the HCCR-1 as a biomarker for HCC, we conducted the prospective cohort study. We evaluated the significance of simultaneous measurement of 2 tumor markers in the diagnosis of HCC in China, Japan and Korea. Two markers for HCC, AFP and HCCR-1, were measured in the sera obtained from 1,338 patients at the time of initial diagnosis of HCC. Of the 1338 HCC patients, 616 (46%) and 686 (51.3%) were sero-positive for AFP and HCCR-1, respectively. The positive rate for HCC was increased up to 74.1% in combined use of AFP and HCCR-1. Many cases (54%) for AFP-negative HCC were positive for HCCR-1 and vice versa. More importantly, the diagnostic rate for small HCC (< 2 cm) was significantly improved in the combined analysis of AFP and HCCR-1 to 56.9% although it was only 40.1% and 23.4% in the single analysis of HCCR-1 and AFP, respectively. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.     

微量离心柱法检测AFP-L3的临床应用研究

目的 探讨微量离心柱法检测甲胎蛋白异质体在肝癌预警及良恶性肝病鉴别诊断中的临床价值.方法 应用装有耦联小扁豆凝集素（LCA）的微量离心柱分离300例肝病患者的AFP-L3,采用化学发光法检测AFP及AFP-L3,计算AFP-L3占总AFP的比率（判断标准以AFP-L3≥10%者为阳性）.结果 AFP-L3在肝细胞癌患者组中的阳性率是95%,在慢性肝病患者组的阳性率是64%,两组患者AFP-L3阳性率差异有统计学意义（x2=134.72,P＜0.01）;AFP-L3阳性的慢性肝病患者与阴性患者肝癌发生率差异有统计学意义（x2=80.158,P＜0.01）;AFP-L3的百分比与AFP浓度不相关（r=0.046,P＞0.05）.结论 微量离心柱法检测甲胎蛋白异质体（AFP-L3）在肝细胞癌诊断、预警及与良恶性肝病的鉴别诊断中具有重要价值.     

Clinical utility of alpha fetoprotein and HCCR-1, alone or in combination, in patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma

Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma (HCC). However, it has been indicated that HCCR-1 (human cervical cancer oncogene 1) might be supplementary to AFP in the detection. We conducted a prospective study in 120 normal and 524 liver disease patients to evaluate the significance of simultaneous measurement of 2 tumor markers (AFP and HCCR-1) in the diagnosis of HCC through the cohort study in Korea and China. We also performed immunohistochemical studies using 25 normal subjects (N), 32 liver cirrhosis (LC) and 116 HCC tissues. The sensitivities of AFP (20 ng/mL) and HCCR-1 (10 ng/mL) in HCC were 55.8% (164/294) and 44.2% (130/294), respectively. When AFP was combined with HCCR-1, sensitivities increased to 4.2% (N), 12.7% (chronic hepatitis; CH), 50.0% (LC), and 77.2% (HCC), respectively. Although there was no significant difference in the diagnostic rate for HCC between AFP and HCCR-1, many cases for AFP-negative HCC were positive for HCCR-1 and vice versa. Moreover, the combined use of AFP and HCCR-1 improved the diagnostic rate to 70.8% in small HCC (< 2 cm) and 81.6% in large HCC (≥ 2 cm), respectively. AFP and HCCR-1 are independent markers. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.     

Usefulness of the Novel Oncofetal Antigen Glypican-3 for Diagnosis of Hepatocellular Carcinoma and Melanoma

Glypican-3 (GPC3) mRNA and protein are expressed in >80% of human hepatocellular carcinomas (HCC) but not in normal tissues except for placenta and fetal liver. The oncofetal antigen GPC3 is a glycosylphosphatidyl inositol-anchored membrane protein and may be secreted. It is a novel tumor marker for human HCC: GPC3 protein was present in sera from 40-50% of HCC patients, but was not detected in sera from patients with liver cirrhosis or chronic hepatitis, or in sera from healthy individuals. alpha-Fetoprotein (AFP) and PIVKA-II (protein induced by vitamin K absence or antagonist-II), are well known major tumor markers for HCC. Generally, AFP shows high positivity for HCC but also high false-positivity in detection assays. Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) is a recently described marker of HCC. Detection of AFP-L3 shows a much higher specificity than AFP, but a lower sensitivity. On the other hand, detection of PIVKA-II shows a lower false-positivity, but is not always sensitive enough to detect low levels secreted by small HCCs. There was no correlation between the three tumor markers, AFP, PIVKA-II, and GPC3 in terms of their presence in HCC cells. All three tumor markers showed similar positivity in patients with HCC, detecting 80% of patients with the disease. GPC3 is also a novel tumor marker for the diagnosis of human melanoma, especially in the early stages of the disease. Expression of GPC3 mRNA and protein was evident in tumor cells from >80% of patients with melanoma and melanocytic nevus, which is a common benign lesion. GPC3 protein was detected in sera from 40% (36/91) of melanoma patients, but not in sera from those with large congenital melanocytic nevus, or from healthy donors. Surprisingly, we detected serum GPC3 even in patients with stage 0, in situ melanoma. The positive detection rate of serum GPC3 at stage 0, I, and II (44.4%, 40.0%, 47.6%, respectively) was significantly higher than that of 5-S-cysteinyldopa, a well known tumor marker for melanoma (0.0%, 8.0%, and 10.0%, respectively). Interestingly, GPC3 was highly immunogenic in mice and elicited effective anti-tumor immunity with no evidence of autoimmunity. Thus, GPC3 is useful for diagnosis of HCC and melanoma and may also have a role in immunotherapy or tumor prevention. However, studies in humans are warranted.     

An Easy and Useful Noninvasive Score Based on α-1-acid Glycoprotein and C-Reactive Protein for Diagnosis of Patients with Hepatocellular Carcinoma Associated with Hepatitis C Virus Infection

This study aimed to evaluate the diagnostic value of α-1-acid glycoprotein (AGP) and C-reactive protein (CRP) and develop a predictive score to improve the diagnosis of hepatocellular carcinoma (HCC). AGP and CRP were measured in serum of 53 HCC patients and 20 liver cirrhosis (LC) patients, in addition to 15 healthy individuals. Area under receiver-operating characteristic curves (AUCs) was used to create a predictive score comprising AGP, CRP, alpha fetoprotein, and albumin. The diagnostic performances of score was determined and compared with AFP alone for the diagnosis of HCC. The combination of AGP, albumin, CRP, and AFP had AUC 0.92 and sensitivity 85% which was higher than AFP alone. The odds ratio of having HCC was 8.4 for AGP, 5.8 for CRP, 12.5 for AFP and 6.5 for albumin. Our score predicted HCC with an OR of 50.6 for HCC. The AUC of score in HCC with single tumor, absent vascular invasion and CLIP score (0–1) were 0.9, 0.9, 0.82, respectively, compared with 0.71, 0.71, 0.68, respectively, for AFP. In conclusion, a non-invasive and simple score based on AGP, CRP, AFP, and albumin could improve the accuracy of HCC diagnosis.