Serum tumor markers for detection of hepatocellular carcinoma

Hepatocellular carcinoma （HCC） is one of the most frequent malignant tumors and is the second most common cause of cancer death in China. Therefore, it is very important to detect this disease and the recurrence at its earlier period. Serum tumor markers, as the effective method for detecting hepatocellular carcinoma for a long time, could be divided into 4 categories： oncofetal antigens and glycoprotein antigens; enzymes and isoenzymes; genes; and cytokines. Serum alpha fetoprotein （AFP） is the most widely used tumor marker in detecting patients with hepatocellular carcinoma, and has been proven to have capability of prefiguring the prognosis. However, it has been indicated that AFP-L3 and DCP excel AFP in differentiating hepatocellular carcinoma from nonmalignant hepatopathy and detecting small hepatocellular carcinoma. Some tumor markers, such as human cervical cancer oncogene and human telomerase reverse transcriptase mRNA, have also been indicated to have higher accuracies than AFP. Furthermore, some other tumor markers, such as glypican-3, gamma-glutamyl transferase Ⅱ, alpha-Ifucosidase, transforming growth factor-beta1, tumorspecific growth factor, have been indicated to be available supplementaries to AFP in the detection. AFP mRNA has been shown to correlate with the metastasis and recurrence of HCC, and it may be the most useful marker to prefigure the prognosis. Some other markers, such as gamma-glutamyl transferase mRNA, vascular endothelial growth factor, and interleukin-8, could also be used as available prognostic indicators, and the simultaneous determination of AFP and these markers may detect the recurrence of HCC at its earlier period.

sFRP-4, a potential novel serum marker for chronic hepatitis B-related hepatocellular carcinoma

BACKGROUND：The current methods used for diagnosing hepatocellular carcinoma（HCC）are unsatisfactory.Here,we assessed the serum levels of secreted frizzled related protein 4（s FRP-4）for diagnosing HCC in patients infected with chronic hepatitis B（CHB）.METHODS：In 272 patients with CHB enrolled,142 were pa tients with HCC.Thirty-three healthy subjects were recruited as healthy controls.The CHB patients were assigned to a test group or a validation group based on the time of enrollment. Human antibody arrays were used to screen 15 patients （8 CHB-related HCC patients, 7 CHB patients） for serum mark- ers. Four markers and one candidate marker were assessed in the test group and validation group, respectively. RESULTS： Human antibody assays indicated that the serum levels of sFRP-4 in HCC patients were significantly higher than those in CHB patients （P〈0,05）. Additionally, serum sFRP-4 levels were significantly higher in the HCC patients than those in the non-HCC patients in both test group （79.7 vs 41.3 ng/mL; P〈0.001） and validation group （89.0 vs 39.0 ng/mL; P〈0.001）. Areas under the Receiver Operating Charac- teristic curves （AUCs） for alpha-fetoprotein （AFP） and sFRP-4 were similar in both test group and validation group. In the test group, the combination of sFRP-4 （a sensitivity of 94.4%, a specificity of 60.5% at 46.4 ng/mL） and AFP （a sensitivity of 75.0%, a specificity of 87.2% at 11.3 ng/mL） showed better performance for diagnosing HCC （a sensitivity of 79.2% and a specificity of 95.3%）. The AUC for combined sFRP-4 and AFP increased to 0.941 （95% CI： 0.908-0.975）, and similar results were seen in the validation group. CONCLUSION： sFRP-4 is a candidate serum marker for diagnosing HCC in CHB patients, and the combination of sFRP-4 with AFP may improve the diagnostic accuracy of HCC.

Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma

AIM:To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS:Serum IL-18,IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls. RESULTS:Serum IL-18,IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (< 105 pg/mL) (4 and 11 mo,respectively,P = 0.015). Multivariate analyses showed that serum IL-18 level,but not IL-6 and IL-12 levels,was a significant and independent prognostic factor of survival. CONCLUSION:These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patients with HCC. Thus,the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.

Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum

Objective： Hepatocellular carcinoma （HCC） is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Methods： Lectin affinity chromatography （LAC） was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography （LC） separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. Results： A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain （FGG）, FOS-like antigen 2 （FOSL2）, and a-l, 6-mannosylglycoprotein 6-^-N-acetylglucosaminyltransferase B （MGATSB） were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. Conclusion： A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC.

Circulating adiponectin: a potential prognostic marker for hepatocellular carcinoma

Objective: We planned this study to investigate the relation between serum adiponectin level and hepatocellular carcinoma (HCC): risk, features and prognosis. Methods: The study included 100 patients with HCC and 40 healthy control subjects. Adiponectin levels were determined by an enzyme-linked immunosorbent assay kit. Results: In the subset of patients with compensated cirrhosis, the mean serum adiponectin level was significantly lower in HCC cases compared to healthy controls (88.6 versus 115 ng/mL; P = 0.012). In addition, serum adiponectin levels correlated negatively with tumor size (P = 0.004) and were significantly lower in patients with vascular invasion and distant metastases (P = 0.03 and P = 0.02 respectively). Furthermore, the median overall survival was significantly higher in the high adiponectin group than the low adiponectin group (median 12.5 versus 9.5 months; log rank = 4.6, P = 0.03). Conclusion: Decreased circulating adiponectin level may play a role in the development of HCC and is a potential poor prognostic marker. These data should be validated in further prospective studies. Also the mechanisms by which adiponectin affect the course of HCC need to be clarified.

Diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.

血清DKK1水平对肝细胞癌(HCC)患者预后判断的临床价值

目的评估血清Dickkopf-l（DKKl）水平与肝细胞癌（hepatocellular carcinoma，HCC）患者术后复发转移和预后的相关性。方法收集2011至2012年间72例在复旦大学附属中山医院进行HCC根治切除患者的术前血清以及其中43例术后1个月的血清，随访至2013年10月。采用ELISA方法定量检测HCC患者术前以及术后血清DKKl水平，分析DKKl高、低组患者主要临床相关资料差异，并评价其与患者复发、预后的相关性。结果1年内共有21人发生复发，1年复发率为26．92％。高DKKl组1年无瘤生存率显著低于低DKKl组（50.0％vs．77．8％，P=0．011）。复发低危亚组中高DKKl组复发率高于低DKKl组患者，包括单个肿瘤（73．3％佻．14．0％，P=0．037）、无卫星灶（56．3％vs．14．3％，P=0．034）、无血管侵犯（37．5％叫．12．5％，P：0．002）、BCLC0＋A（53．3％w．15．2％，P：0．010）。两组患者的临床病理特征的差异无统计学意义。多因素结果提示高DKKl为术后无瘤生存的独立预后因素（HR为3．753，95％CI为1．495-9．424，P=0．005）。受试者工作特征曲线分析显示术前血清DKKl水平对预测HCC患者术后复发具有较好的特异性（82．35％）。术后DKKl持续维持在高水平的患者具有更高的复发率（50．0（）％）。结论术前血清高水平DKKl预示HCC患者早期复发率高。血清DKKl水平可有效预测HCC切除术后患者的预后，监测DKKl可以帮助临床制定最有效的HCC治疗方案。

血清学标志物甲胎蛋白、PIVKA-Ⅱ和磷脂酰肌醇蛋白聚糖3联合诊断肝癌的meta分析

目的:探讨血清生物标志物甲胎蛋白(AFP)、维生素K缺失或拮抗剂Ⅱ诱导的蛋白质(PIVKA-Ⅱ)和磷脂酰肌醇蛋白聚糖3(GPC-3)单独或联合用于肝细胞癌(以下简称肝癌)诊断的价值。方法:检索PubMed、Web of Science、Embase三个数据库,收集2002年以来发表的AFP、PIVKA-Ⅱ和GPC-3单独或联合用于诊断肝癌的文献。根据纳入和排除标准筛选文献并提取相关数据。利用诊断准确性研究的质量评价(QUADAS)检查表对纳入的文献进行质量评价,并采用Meta DiSc软件、Review Manager 5.4软件和Stata 15.1软件对AFP、PIVKA-Ⅱ和GPC-3单用和联合使用诊断肝癌的受试者工作特征曲线下面积(AUC)、敏感度、特异度等指标进行数据分析。结果:共纳入32篇文献。Meta分析结果显示,单个标志物用于诊断肝癌时,PIVKA-Ⅱ的AUC值最高,为0.88(95%CI:0.85~0.91),其次是GPC-3和AFP;多个标志物联合用于诊断肝癌的AUC均高于单个标志物,其中PIVKA-Ⅱ联合GPC-3诊断的AUC值最高,为0.90(95%CI:0.87~0.92)。单个标志物用于诊断肝癌时,PIVKA-Ⅱ和GPC-3的敏感度相对较高(分别为0.75和0.76),但GPC-3的特异度不如PIVKA-Ⅱ和AFP(AFP、PIVKA-Ⅱ和GPC-3分别为0.87、0.88和0.81);多个标志物联合用于诊断肝癌的敏感度较单个标志物诊断时有所提高,但特异度无明显提高。单个标志物用于诊断肝癌时,PIVKA-Ⅱ的诊断比值比(DOR)最高,为22(95%CI:13~36),其次是GPC-3和AFP;两个标志物联合用于诊断肝癌的DOR均高于单个标志物,其中AFP联合GPC-3诊断的DOR最高,为25(95%CI:9~67);三个标志物联合用于诊断肝癌时的DOR明显降低,为10(95%CI:7~45)。结论:单个标志物用于肝癌诊断时,PIVKA-Ⅱ的诊断价值更高。两种标志物联合能显著提高肝癌诊断的敏感度,三种标志物联合未能进一步提高诊断价值。结合临床实际,推荐AFP联合PIVKA-Ⅱ用于肝癌的诊断。

lncRNA SLC9A3-AS1在肝细胞癌中的临床意义及生物学功能分析

目的探讨lncRNA SLC9A3-AS1在肝细胞癌(HCC)中的表达意义和其参与HCC发生发展的潜在作用机制。方法收集37例HCC组织及其配对癌旁组织,以及HCC细胞RNA,利用qRT-PCR检测lncRNA SLC9A3-AS1在组织和细胞中的表达水平,并分析其与患者临床病理特征的关系。绘制lncRNA SLC9A3-AS1的受试者工作特征(ROC)曲线,分析其对HCC的诊断效能。通过生物信息学方法筛选与lncRNA SLC9A3-AS1结合的RNA结合蛋白,并绘制韦恩图,分析lncRNA SLC9A3-AS1与结合蛋白表达的相关性,以及蛋白表达与HCC病理分期和患者生存预后的关系。结果lncRNA SLC9A3-AS1在HCC组织和细胞中表达下调,其表达水平与患者血清甲胎蛋白(AFP)水平明显相关(P<0.05)。lncRNA SLC9A3-AS1的ROC曲线下面积(AUC)为0.849(95%CI:0.796~0.886)。韦恩图显示5个与lncRNA SLC9A3-AS1潜在结合的蛋白:hnRNPA1、YTHDC1、RBM4、NONO和RBMx,其表达与lncRNA SLC9A3-AS1表达呈明显正相关(P<0.05)。随着HCC分期的进展,不同分期的RNA结合蛋白表达量差异有统计学意义(P<0.05);RBM4、NONO和RBMx低表达患者总体生存期明显长于高表达患者(P<0.05)。结论lncRNA SLC9A3-AS1在HCC中下调,有望作为HCC诊断的生物标志物,并且可能通过与RNA结合蛋白互作调控HCC进展。

HCC患者多肽生长因子及肿瘤标志物测定的临床意义

目的:分析血清多肽生长因子水平与肝硬化、肝癌的关系,初步探讨其发病机制。方法:采用放射免疫分析(RIA)测定32例肝癌(HCC)、34例肝硬化(LC)患者及30名正常对照组人员的血清TGF-α、TGF-β1、AFP及AFU水平四项指标。结果:HCC患者组血清TGF-α、TGF-β1、AFP及AFU水平均显著高于LC组及正常对照组(P均<0.05),LC组则AFP及AFU水平均显著高于正常对照组(P<0.05),但TGF-α、TGF-β1水平与正常对照组比较无显著性差异(P>0.05)。结论:HCC患者血清多肽生长因子TGF-α、TGF-β1、AFP及α-L、岩藻糖苷酶(AFU)水平发生了明显的变化,提示四项指标水平的升高及过度表达与肝癌的恶性增殖生长、病情的进展关系密切。

Midkine(MDK)在肝细胞癌(HCC)中的表达及其临床意义

目的探讨Midkine(MDK)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达以及检测血清MDK对于肝癌诊断的初步临床意义。方法通过免疫组织化学染色和Western blot法检测50例临床样本(包含肝癌,肝硬化及正常肝组织)及7种不同肝癌细胞系中MDK表达情况;进一步通过酶联免疫吸附反应定量检测120例不同受试人群的血清样本,分析血清MDK在诊断肝癌中的初步临床意义。结果肝癌组织中MDK表达阳性率显著高于肝硬化(77%vs.30%,P<0.01)及正常肝组织(77%vs.0%,P<0.001);Western blot检测结果显示,MDK在多株肝癌细胞系中表达上调;此外,HCC患者血清MDK的中位数水平(1.195 ng/mL,0.84～1.71)较正常人(0.102 ng/mL,0.02～0.53;P<0.01)、HBV相关肝硬化(0.57 ng/mL,0.26～0.67;P<0.05)和HCV相关肝硬化(0.34 ng/mL,0.09～0.56;P<0.01)患者显著升高。结论 MDK在HCC患者中的表达显著上调,血清检测MDK可作为临床诊断肝癌的重要方法。

ELISA法检测血清中抗CNN2抗体的实验条件优化性探讨

目的探讨血清抗钙调节蛋白Calponin 2(CNN2)抗体的最适酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)实验条件。方法将BL21(DE3)p Lys S-pColdⅢ-C基因工程菌重组表达而分离纯化的CNN2包被至酶标板。采集肝细胞癌患者血清和正常人血清,探讨蛋白包被浓度、血清稀释液的选择、封闭方式及条件的选择、HRP标记亲和素稀释度的最适条件。结果CNN2蛋白浓度为10μg/ml时为最适蛋白包被浓度。0.5%胎牛血清蛋白(BSA)为最适封闭方式。使用PBST来稀释血清,成本低,效果好。亲和素的最适稀释比为1∶9000。最适实验条件的重复性良好。ROC曲线分析结果显示,最适实验条件下,该检测方法ROC曲线下面积(AUC)为0.978(95%CI:0.947~1.000,P=0.000);截断值为0.484,其对应的灵敏度为96.0%,特异度为93.0%。结论构建了检测血清抗CNN2抗体的最适ELISA实验条件。

GP73的血清学分析以及联合AFP在HCC中的诊断价值

目的探讨不同人群血清中GP73水平及分析GP73和AFP联合检测对原发性肝细胞癌诊断的临床价值。方法收集119例原发性肝癌患者、50例肝硬化患者、114例慢性乙肝患者、6例慢性乙肝携带者及139例健康人血清,采用ELISA的方法对每个样本中GP73含量进行检测,结合各项临床指标进行统计学分析。结果血清GP73水平在健康人群中呈正态分布,而且在男性与女性之间无统计学差异(P>0.05)。分析HCC组血清中GP73水平发现,男性患者高于女性患者(P=0.013),伴有肝硬化的患者高于无肝硬化的患者(P=0.002),肿瘤直径>3cm的患者高于肿瘤直径≤3cm的患者(P=0.041),而GP73水平与HCC患者的年龄、AFP、ALT、AST、巴塞罗那(BCLC)分级、是否HBV感染、肿瘤数目无显著相关性。血清中GP73检测的阳性临界值为61.93ng/mL。根据这一临界值得出,GP73诊断HCC患者的灵敏度和特异度分别为58.82%和98.56%。GP73阳性率较高的是肝硬化患者组(86%)和慢性乙肝患者组(76.32%),HCC组的阳性率为58.82%,健康人群的GP73阳性率为1.44%,慢性乙肝携带者中未检出阳性样本。结合临床数据,GP73联合AFP检测的阳性率为82.35%。结论GP73在HCC患者血清中表达较高,将其作为一种肝癌血清标志物具有很好的研究价值;血清中GP73联合AFP检测的方法可有效提高对HCC的诊断率,从而避免漏诊现象的发生,对HCC的诊断具有重要的参考价值。

免疫检查点抑制剂治疗肝细胞癌的研究进展

肝癌的发病率及死亡率在全球恶性肿瘤中均位居前列。初诊的肝细胞癌(hepatocellular carcinoma,HCC)患者大多已处于晚期,失去手术根治的机会,全身治疗成为主要的治疗手段。随着免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的出现,多种ICIs被批准用于晚期HCC患者,ICIs联合抗血管生成药物为主的靶向药物的治疗方案也被证实比ICIs单药效果更佳。但是,无论是单药ICIs还是联合治疗方案,多数患者仍不能从中获益。根据患者治疗的不同目标,通过肿瘤标记物选择不同的治疗方案是目前临床面临的挑战。本文对目前ICIs以及联合不同药物和局部治疗在HCC的临床研究进展、预测疗效和预后的生物标记物以及耐药性相关问题进行综述。

Precision diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common type of primary hepatocellular carcinoma(PHC).Early diagnosis of HCC remains the key to improve the prognosis.In recent years,with the promotion of the concept of precision medicine and more in-depth analysis of the biological mechanism underlying HCC,new diagnostic methods,including emerging serum markers,liquid biopsies,molecular diagnosis,and advances in imaging(novel contrast agents and radiomics),have emerged one after another.Herein,we reviewed and analyzed scientific advances in the early diagnosis of HCC and discussed their application and shortcomings.This review aimed to provide a reference for scientific research and clinical practice of HCC.

解表剂桂枝汤加味治疗晚期肝癌合并腹水的临床疗效及对血清炎症因子影响分析

【目的】分析解表剂桂枝汤加味治疗晚期肝癌合并腹水的临床疗效及对血清炎症因子的影响。【方法】通过便利抽样、对照原则回顾性收集2020年1月至2022年1月期间在新乡市中心医院住院治疗的100例晚期肝癌合并腹水患者,根据治疗方法的不同分为观察组和对照组,每组各50例。对照组给予常规西药治疗,观察组在对照组的基础上给予解表剂桂枝汤加味治疗,疗程为21 d。观察2组患者治疗前后腹围、Karnofsky功能状态(KPS)评分、血清炎症因子、肝功能、血清肿瘤标志物的变化情况,并评价2组患者的临床疗效。【结果】(1)治疗21 d后,观察组的总有效率为84.00%(42/50),对照组为60.00%(30/50),组间比较,观察组的疗效明显优于对照组(P<0.01)。(2)观察组治疗1周、2周、3周后及对照组治疗2周、3周后的腹围均较治疗前降低(P<0.05),KPS评分均较治疗前升高(P<0.05),且治疗组在治疗1周、2周、3周后对腹围的降低作用及对KPS评分的升高作用均明显优于对照组(P<0.01)。(3)观察组治疗1周、2周、3周后及对照组治疗2周、3周后的血清白细胞介素1β(IL-1β)、C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、癌胚抗原125(CA125)、甲胎蛋白(AFP)水平均较治疗前明显降低(P<0.05),且观察组在治疗1周、2周、3周后对上述指标的降低作用均明显优于对照组(P<0.05或P<0.01)。【结论】在常规西药治疗基础上配合解表剂桂枝汤加味治疗,可有效减少腹水量,缩小腹围,提高治疗效果,减轻炎症反应,降低血清肿瘤标志物水平,改善患者肝功能及生存状况,具有一定的临床价值。

腹腔镜肝部分切除术治疗肝癌的近远期疗效的影响

目的探究腹腔镜肝部分切除术治疗肝癌的近远期疗效及对血清肿瘤标志物影响。方法回顾性分析2014年2月~2017年2月72例原发性肝癌患者临床资料,根据手术方式不同分为腹腔镜组39例(腹腔镜肝部分切除术)与开腹组33例(开腹肝部分切除术),比较两组围术期情况、围术期肝功能指标[血清总胆红素(TBIL)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)]、手术前后血清肿瘤标志物[甲胎蛋白(AFP)同型半胱氨酸(Hey)、甲胎蛋白异质体3(AFP-L3)]、术后并发症发生率,随访3年,记录患者复发情况及3年总生存率。结果腹腔镜组切口长度、术中出血量、术后禁食时间、绝对卧床时间及住院时间均显著小于或短于开腹组(P<0.05);术后第ld第5d,两组血清TBIL、AST、ALT水平呈先升高后下降趋势,且腹腔镜组术后第5d血清TBIL、AST、ALT水平均显著低于开腹组(P<0.05);术后第7d、1个月,两组血清AFP、Hey、AFP-L3水平均呈明显低于术前(P<0.05),但腹腔镜组与开腹组同时间点血清AFP、Hey、AFP-I3水平比较差异均无统计学意义(P>0.05);腹腔镜组并发症总发生率5.13%,低于开腹组的27.27%(P<0.05);随访3年内,腹腔镜组复发率35.90%.3年总生存率为74.36%,与开腹组的33.33%.69.70%比较差异均无统计学意义(P>0.05)。结论腹腔镜肝部分切除术与开腹肝部分切除术治疗肝癌远期疗效相当,但前者可减小手术创伤、降低术后并发症发生率,利于患者早期恢复。

Expert consensus on the role of hematological markers in the earlyclinical screening of hepatocellular carcinoma

The disease burden of hepatocellular carcinoma (HCC) in China is heavy, and the prognosis is stillunfavourable. Therefore, early screening of high-risk groups of HCC through simple methods is the key toachieving early diagnosis and treatment and improving survival. At present, alpha-fetoprotein and otherhematological tests are still the main methods in the early screening of HCC, but the sensitivity andspecificity are limited, and the risk of missed diagnosis is high. In recent years, with the continuousdevelopment of science and technology, the improvement of traditional detection methods and theemergence of novel markers such as methylated deoxyribonucleic acid and microRNA have brought hopefor further improving the sensitivity and specificity of early HCC screening. This consensus summarizesthe research progress of traditional and new hematological test methods and puts forward expertguidance on the role of hematological markers in the early screening of HCC to provide a basis forimproving the prevention and control level in China.

AFP在早期肝癌诊断中的临床价值研究

目的探讨血清肿瘤标记物甲胎蛋白(AFP)在早期肝癌诊断中的临床价值。方法采用电化学发光法,检测71例肝硬化患者、46例早期肝癌患者、25例中晚期肝癌患者血清甲胎蛋白含量,并分析其与肝癌的临床病理特点之间的关系。结果肝硬化组血清log AFP水平为(0.99±0.43)ng/ml,早期肝癌组为(1.79±0.84)ng/ml,晚期肝癌组为(2.66±1.24)ng/ml,3组比较差异有统计学意义(P<0.05);早期肝癌组与中晚期肝癌组log AFP比较,差异有统计学意义(P<0.05),中晚期肝癌组AFP水平高于早期肝癌组。血清AFP水平与肿瘤体积呈正相关(P<0.05)。应用受试者工作特征曲线分析并确定早期肝癌诊断的最佳临界值,曲线下面积为0.824,最佳临界值为15.315 ng/ml,灵敏性为80.4%,特异性为69%。结论 AFP对于早期肝癌的诊断,具有重要的临床价值,在临界浓度为15.315 ng/ml时能提高早期肝癌诊断的灵敏性。

高尔基蛋白73单克隆抗体在肝细胞肝癌诊断中的价值

目的自制高尔基蛋白73(GP73)单克隆抗体并检测其诊断肝细胞肝癌(HCC)的敏感性和特异性。方法自行制备GP73单克隆抗体,作为一抗用Western blot方法检测59例HCC患者和31名健康对照者血清中GP73蛋白的表达情况,并对结果进行半定量分析,确定对照组人群的正常基线水平。将此结果同多克隆抗体的检测结果及甲胎蛋白(AFP)的诊断结果进行比较。结果使用单克隆抗体检测健康人群的血清GP73水平为1.2(0.9-1.7)相对单位(RU),HCC患者血清GP73水平为5.7(2.5-7.8)RU,显著高于对照组水平(P<0.001);多克隆抗体检测结果显示,HCC患者血清GP73水平与对照组相比[7.8(3.0-12.4)RU比1.1(1.0-2.0)RU]亦显著增高(P<0.001)。GP73单抗诊断HCC的敏感性和特异性分别为84.7%和93.5%,对比多抗的敏感性(78.0%)和特异性(93.5%),前者敏感性有所增高;同组患者采用AFP诊断HCC的敏感性和特异性分别为67.8%和74.2%,均低于GP73单抗。Logistic回归分析显示,GP73单抗的优势比(OR)为7.18,而GP73多抗的OR为1.51。结论单克隆抗体可以有效地检测肝癌患者血清GP73水平,比AFP具有更高的敏感性和特异性;可能优于目前使用的GP73多克隆抗体的检测。这一结果为用自制单抗进一步开发酶联免疫方法检测奠定了基础。