Clinical features of abnormalα-fetoprotein in 15 patients with chronic viral hepatitis B after treatment with antiviral drugs

BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.

Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma

AIM:To explore the relationship between α-fetoprotein(AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma(HCC) thoroughly.METHODS:A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study.The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis,such as status of hepatitis B virus(HBV) infection,tumor size,tumor number,vascular invasion and degree of tumor differentiation.Also,patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP(≤ 20 μg/L,21-400 μg/L,401-800 μg/L,and ≥ 801 μg/L),to compare the positive rate of patient among four groups stratified by various clinicopathological variables.And the correlation of different kinds of tumor staging systems,such as TNM,Barcelona Clinic Liver Cancer(BCLC) staging classification and China staging,were compared with the serum concentration of AFP.RESULTS:A total of 2304 HCC patients were enrolled in this study totally;the mean serum level of AFP was 555.3 ± 546.6 μg/L.AFP levels were within the normal range(< 20 μg/L) in 27.4%(n = 631) of all the cases.81.4%(n = 1875) patients were infected with HBV,and those patients had much higher serum AFP level compared with non-HBV infection ones(573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L,P < 0.001).The AFP level in tumors ≥ 10 cm(808.4 ± 529.2 μg/L) was significantly higher(P < 0.001) than those with tumor size 5-10 cm(499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm(444.9 ± 514.2 μg/L).AFP levels increased significantly in patients with vascular invasion(694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L,P < 0.001).Patients with low tumor cell differentiation(559.2 ± 545.7 μg/L) had the significantly(P = 0.007) highest AFP level compared with high differentiation(207.3 ± 420.8 μg/L) and intermediate differentiation(527.9 ± 538.4 μg/L).In the multiple variables analysis,low tumor cell differentiation [OR 6.362,95%CI:2.891-15.382,P = 0.006] and tumor size(≥ 10 cm)(OR 5.215,95%CI:1.426-13.151,P = 0.012) were independent predictors of elevated AFP concentrations(AFP > 400 μg/L).Serum AFP levels differed significantly(P < 0.001) in the D stage of BCLC(625.7 ± 529.8 μg/L) compared with stage A(506.2 ± 537.4 μg/L) and B(590.1 ± 551.1 μg/L).CONCLUSION:HCC differentiation,size and vascular invasion have strong relationships with AFP,poor differentiation and HCC size ≥ 10 cm are independent predictors of elevated AFP.BCLC shows better relationship with

Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients

AIM:To clarify the utility of using des-γ-carboxy prothrombin(DCP)andα-fetoprotein(AFP)levels to predict the prognosis of hepatocellular carcinoma(HCC)in patients with hepatitis B virus(HBV)and the hepatitis C virus(HCV)infections.METHODS:A total of 205 patients with HCC(105patients with HBV infection 100 patients with HCV infection)who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively.Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy,and cutoff levels were calculated.Patients in the HBV and HCV groups were classified into three groups:a group with low AFP and DCP levels(LL group),a group in which one of the two parameters was high and the other was low(HL group),and a group with high AFP and DCP levels(HH group).Liver function parameters,the postoperative recurrence-free survival rate,and postoperative overall survival were compared between groups.The survival curves were compared by logrank test using the Kaplan-Meier method.Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis.RESULTS:The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/m L and 60 m AU/m L,respectively;for preoperative DCP levels,the cutoff levels were 21.0 ng/m L in the HBV group and 67 m AU/m L in the HCV group.The HBV group was significantly different from the other groups in terms of vascular invasion,major hepatectomy,volume of intraoperative blood loss,and surgical duration.Significant differences were found between the LL group,the HL group,and the HH group in terms of both mean disease-free survival time(MDFST)and mean overall survival time(MOST):64.81±7.47 vs 36.63±7.62 vs 18.98±6.17mo(P=0.001)and 85.30±6.55 vs 59.44±7.87 vs46.57±11.20 mo(P=0.018).In contrast,the HCV group exhibited a significant difference in tumor size,vascular invasion,volume of intraoperative blood loss,and surgical duration;however,no significant difference was observed between the three groups in liver function parameters except for albumin levels.In the LL group,the HL group,and the HH group,the MDFST was 50.09±5.90,31.01±7.21,and 14.81±3.08 mo(log-rank test,P<0.001),respectively,and the MOST was 79.45±8.30,58.82±7.56,and 32.87±6.31 mo(log-rank test,P<0.001),respectively.CONCLUSION:In the HBV group,the prognosis was poor when either AFP or DCP levels were high.In the HCV group,the prognosis was good when either or both levels were low;however,the prognosis was poor when both levels were high.High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups.The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.

Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma

AIM To determine the prevalence and diagnostic value of autoantibodies inα-fetoprotein(AFP)-negative hepatocellular carcinoma(HCC).METHODS Fifty-six serum samples from AFP-negative HCC cases,86 from AFP-positive HCC cases,168 from chronic liver disease cases,and 59 from normal human controls were included in this study.Autoantibodies to nucleophosmin(NPM)1,14-3-3zeta and mouse double minute 2 homolog(MDM2)proteins in AFP-negative HCC serum were evaluated by enzymelinked im munosorbent assay.Partially positive sera were further evaluated by western blotting.Immunohistochemistry was used to detect the expression of three tumor-associated antigens(TAAs)in AFP-negative HCC and normal control tissues.RESULTS The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%,19.6%and 19.6%,which was significantly higher than in the chronic liver disease cases and normal human controls(P<0.01)as well as AFP-positive HCC cases.The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6%to 21.4%,and the specificity was approximately 95%.When the three autoantibodies were combined,the sensitivity reached 30.4%and the specificity reached 91.6%.CONCLUSION Autoantibodies to NPM1,14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.

Is inconsistency of α-fetoprotein level a good prognosticator for hepatocellular carcinoma recurrence?

AIM: To identify the clinical outcomes of hepato-cellular carcinoma (HCC) patients with inconsistent α-fetoprotein (AFP) levels which were initially high and then low at recurrence.METHODS: We retrospectively included 178 patients who underwent liver resection with high preoperative AFP levels (≥ 200 ng/dL). Sixty-nine HCC patients had recurrence during follow-up and were grouped by their AFP levels at recurrence: group Ⅰ, AFP ≤ 20 ng/dL (n = 16); group Ⅱ, AFP 20-200 ng/dL (n = 24); and group Ⅲ, AFP ≥ 200 ng/dL (n = 29). Their preoperative clinical characteristics, accumulated recurrence rate, and recurrence-to-death survival rate were compared. Three patients, one in each group, underwentliver resection twice for primary and recurrent HCC. AFP immunohistochemistry of primary and recurrent HCC specimens were examined.RESULTS: In this study, 23% of patients demon-strated normal AFP levels at HCC recurrence. The AFP levels in these patients were initially high. There were no significant differences in clinical characteristics between the three groups except for the mean recur-rence interval (21.8 ± 14.6, 12.3 ± 7.7, 8.3 ± 6.6 mo, respectively, P < 0.001) and survival time (40.2 ± 19.9, 36.1 ± 22.4, 21.9 ± 22.0 mo, respectively, P = 0.013). Tumor size > 5 cm, total bilirubin > 1.2 mg/dL, vessel invasion, Child classification B, group Ⅲ, and recurrence interval < 12 mo, were risk factors for survival rate. Cox regression analysis was performed and vessel invasion, group Ⅲ, and recurrence interval were independent risk factors. The recurrence inter-val was significant longer in group Ⅰ (P < 0.001). The recurrence-to-death survival rate was significantly bet-ter in group Ⅱ (P = 0.016). AFP staining was strong in the primary HCC specimens and was reduced at recur-rence in group Ⅰ specimens.CONCLUSION: Patients in group Ⅰ with inconsistent AFP levels had a longer recurrence interval and worse recurrence-to-death survival rate than those in group Ⅱ. This clinical presentation may be caused by a delay in the detection of HCC recurrence.

α-fetoprotein,vascular endothelial growth factor receptor-1 and early recurrence of hepatoma

AIM:To investigate whether α-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocel-lular carcinoma (HCC).METHODS:From 2000 to 2005,114 consecutive pa-tients with HCC underwent primary curative hepatecto-my.The mean age was 60.7 (8.7) years and 94 patients were male.The median follow-up period was 71.2 mo (range:43-100 mo).Immediately prior to commencing laparotomy,5 mL bone marrow was aspirated from thesternum and collected in citrate-coated test tubes.The initial 2 mL of bone marrow aspirate was discarded in each case.AFP mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM-and PH-AFP mRNA and BM-and PH-VEGFR-1 mRNA,respectively) were measured by real-time quantitative reverse transcription polymerase chain reaction.As normal controls,VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver donors.These data were evaluated for any correlation with early recurrence,comparing clinical and pathological outcomes.RESULTS:The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 × 10-7 and zero,respectively,based on data from the controls.A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA,respectively.The BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal con-trols,and this was the case also for PH-VEGFR-1mRNA.The 25-percentile values for the BM-and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript levels.The High group for BM-VEG-FR-1 mRNA contained 81 (71.1%) HCC cases and the Low group was assigned 33 (28.9%) patients.These numbers for PH-VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%),respectively.HCC recurred in 80 patients;in the remnant liver in 48 cases,in the remnant liver and remote tissue in 20,and in the remote tissue alone in 12.BM-AFP mRNA-positive cases showed a signifi-cantly higher rate of early recurrence (within 1 year of surgical treatment) compared with BM-AFP mRNA-negative patients (P=0.0091).Patients were classified into four groups according to the level/status of their BM-VEGFR-1 and BM-AFP mRNA as follows:group A (n=23),BM-VEGFR-1/BM-AFP mRNA=low/negative;group B (n=57) high/negative;group C (n=10) low/positive;group D (n=24),high/positive.This classifi-cation was found to correlate with a recurrence of thisdisease within 1 year (P=0.0228).The disease-free survival curve of group A was significantly better than that of groups B,C or D (P=0.0437,P=0.0325,P=0.0225).No other classification (i.e.,PH-VEGF-R1/BM-AFP,BM-VEGF-R1/PH-AFP,and PH-VEGF-R1/PH-AFP mRNA) showed such a correlation.CONCLUSION:The evaluation of BM-AFP and BM-VEG-FR-1 mRNA in patients with HCC may be a valuable pre-dictor of disease recurrence following curative resection.

Possible connection between elevated serum α-fetoprotein and placental necrosis during pregnancy: A case report and review of literature

Placenta previa is the main cause of bleeding throughout pregnancy,and it is associated with serious complications,such as infection,that lead to a poor prognosis.Gynecological sonography is recommended as the first-line examination technique for the surveillance and determination of vaginal bleeding and for early intervention.We report the case of a patient with gradually expanded hypoechoic lesion and extremely high serumα-fetoprotein level during her third trimester,and discuss their potential relationship in evaluating the progression of placental necrosis.

Gastric choriocarcinoma admixed with an α-fetoprotein-producing adenocarcinoma and separated adenocarcinoma

We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adeno-carcinoma. A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum. The patient underwent radical subtotal gastrectomywith D2 lymph node dissection and Billroth gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively.

Highlights for α-fetoprotein in determining prognosis and treatment monitoring for hepatocellular carcinoma

AIM:To explore the prognostic value in the monitoring of treatment efficacy of serial α-fetoprotein(AFP) in hepatocellular carcinoma(HCC) patients.METHODS:We searched MEDLINE,EMBASE and COCHRANE LIBRARY through April 21,2012,to find qualifying articles.Our overall search strategy included terms for HCC,AFP,treatment response,and prognosis.Literature was limited to English-language,human studies.Studies reporting cumulative survival rates were summa-rized qualitatively.For the prognostic meta-analysis,we undertook a series of meta-analyses that summarised the Cox proportional hazard ratios(HRs) by assuming a random effects model.With regards to the correlation of AFP change with radiologic response,the categorical dichotomous variables were assessed using Poisson relative risks(RRs),which were incorporated into the random effects model meta-analysis of accuracy prediction.Between-study heterogeneity was estimated by use of the I2 statistic.Publication bias was evaluated using the Begg funnel plot and Egger plot.Sensitivity analyses were conducted first by separating systemic treatment estimates from locoregional therapy estimates,evaluating different AFP response cut-off point effects,and exploring the impact of different study sizes.RESULTS:Of 142 titles identified in our original search,11 articles(12 clinical studies) met our criteria.Six studies investigated outcome in a total of 464 cases who underwent systemic treatment,and six studies investigated outcome in a total of 510 patients who received locoregional therapy.A random-effects model metaanalysis showed that AFP response was associated with an mortality HR of 0.55(95%CI,0.47-0.65) across HCC in overall survival(OS) and 0.50(95%CI,0.38-0.65) in progression-free survival.Restricting analysis to the six eligible analyses of systemic treatment,the pooled HRs were 0.64(95%CI,0.53-0.77) for OS.Limiting analysis to the six analyses of locoregional therapy,the pooled HRs for OS was 0.39(95%CI,0.29-0.53).We showed a larger pooled HR in the 50% definition studies(HR,0.67,95%CI,0.55-0.83) compared with that from the 20% definition studies(HR,0.41,95%CI,0.32-0.53).Restricting analysis to the four studies including over 100 patients individually,the pooled HR was 0.65(95%CI,0.54-0.79),with a pooled HR for OS of 0.35(95%CI,0.23-0.46) in the studies of less than 100 patients.As to radiological imaging,43.1%(155/360) of the patients in the AFP response group presented with a radiological overall response,while the response rate decreased to 11.5%(36/313) in the patients from theAFP nonresponse group.The RR of having no overall response was significantly lower in the AFP response group than the AFP nonresponse group(RR,0.67;95%CI,0.61-0.75).In terms of disease control rate,86.9%(287/330) in the AFP response group and 51.0%(153/300) in the AFP nonresponse group showed successful disease control,respectively.The RR of disease control failure,similarly,was significantly lower in the AFP response group(RR,0.37;95%CI,0.23-0.58).But these findings could be overestimates because of publication and reporting bias.CONCLUSION:HCC patients presenting with an AFP response are at decreased risk of mortality.In addition,patients with an AFP response also present with a higher overall response rate and disease control rate.

Gene Cloning of Murine α-Fetoprotein Gene and Construction of Its Eukaryotic Expression Vector and Expression in CHO Cells

To clone the murine α fetoprotein (AFP) gene, construct the eukaryotic expression vector of AFP and express in CHO cells, total RNA were extracted from Hepa 1 6 cells, and then the murine α fetoprotein gene was amplified by RT PCR and cloned into the eukaryotic expression vector pcDNA3.1. The recombinant of vector was identified by restriction enzyme analysis and sequencing. After transient transfection of CHO cells with the vector, Western blotting was used to detect the expression of AFP. It is concluded that the 1.8kb murine α fetoprotein gene was successfully cloned and its eukaryotic expression vector was successfully constructed.

A novel α-fetoprotein-MIP immunosensor based on AuNPs/PTh modified glass carbon electrode

A new α-fetoprotein-MIP(AFP-MIP) immunosensor based on glass carbon electrode(GCE) modified with polythionine(PTh) and gold nanoparticles(AuNPs) was successfully fabricated for sensitive detection ofα-fetoprotein(AFP). Through controlling electropolymerization, A "polydopamine(PDA)-AFP" complex was achieved applying AFP as template and dopamine(DA) as imprinted monomers. After elution, the specific cavities can adsorb the target molecules. Using differential pulse voltammetry(DPV) detection,the peak current decreased with the increase in concentration of AFP, and the linear response range of the AFP-MIP immunosensor was from 0.001 ng/mL to 800 ng/mL with the detection limit as low as0.8138 pg/mL. The MIP immunosensor could become a new promising method for the detection of AFP.Furthermore, this MIP sensor was demonstrated in testing AFP in human serum samples with satisfactory results.

Expression of β-catenin Protein in Hepatocellular Carcinoma and Its Relationship with Alpha-fetoprotein

This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma（HCC） tissues and its relationship with α-fetoprotein（AFP） in HCC.Immunohistochemistry was used to determine the expression of β-catenin in normal liver tissues（n=10）,liver cirrhosis tissues（n=20）,and primary HCC tissues（n=60）.The relationship between β-catenin expression and clinical parameters of HCC was investigated.Real-time PCR and Western blotting were used to detect the m RNA and protein expression levels of β-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP,and also the m RNA and protein expression levels of β-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP sh RNA plasmids.The results showed that β-catenin was only expressed on the cell membrane in normal liver tissues.Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues,and such ectopic expression of β-catenin was predominant in HCC tissues.The abnormal expression of β-catenin was correlated with serum AFP levels,cancer cell differentiation and vascular invasion（P〈0.05）.Additionally,the increased expression of AFP resulted in the upregulation of β-catenin m RNA and protein levels,while knockdown of AFP with AFP sh RNA led to significantly decreased β-catenin m RNA and protein levels（P〈0.05）.It was suggested that the abnormal expression of β-catenin is implicated in hepatic carcinogenesis and development.AFP can lead to increased expression of β-catenin,which may account for the poor prognosis of AFP-associated HCC patients.

载药微球联合TACE治疗原发性肝癌患者的效果观察

目的观察载药微球联合肝动脉化疗栓塞术(TACE)治疗原发性肝癌患者的效果。方法选取2021年6至12月收治的原发性肝癌患者60例,根据患者住院序号分为研究组和对照组各30例。研究组采用TACE联合CalliSpheres载药微球治疗,对照组接受传统TACE治疗。观察2组临床疗效、血常规、肝功能指标、甲胎蛋白(AFP)水平,并评估安全性。结果2组治疗后血红蛋白、血小板计数、白蛋白较治疗前降低,总胆红素、丙氨酸转氨酶、天冬氨酸转氨酶较治疗前升高(P<0.05);2组治疗后1周上述指标比较差异无统计学意义(P>0.05)。研究组治疗后AFP水平低于对照组(P<0.05)。研究组并发症及毒副反应发生率低于对照组(P<0.05)。研究组总有效率[86.67%(26/30)]高于对照组[63.33%(19/30)](P<0.05)。研究组术后1、2年的总体生存与局部控制率均高于对照组(P<0.05)。研究组满意度评分[(79.14±16.37)分]高于对照组[(64.35±17.22)分](P<0.01)。结论载药微球联合TACE治疗原发性肝癌效果较好,可有效延长患者生存时间,减轻并发症及毒副反应,提高生存质量。

丙型病毒性肝炎肝癌患者丙型肝炎病毒-RNA载量与甲胎蛋白、癌胚抗原的关系

目的探讨丙型病毒性肝炎肝癌患者丙型肝炎病毒(HCV)-RNA载量与甲胎蛋白(AFP)、癌胚抗原(CEA)的关系。方法选取37例丙型病毒性肝炎肝癌患者,使用全自动化学发光测定仪检测血清CEA、AFP水平,采用荧光定量聚合酶链反应法检测HCV-RNA载量,根据HCV-RNA载量检测结果分为HCV高载量组(n=20)和HCV低载量组(n=17),比较两组患者的CEA、AFP水平。采用Spearman相关性分析法分析HCV-RNA载量与CEA、AFP的相关性。采用受试者工作特征(ROC)曲线及曲线下面积(AUC)分析CEA、AFP单独及联合检测对HCV-RNA高载量丙型病毒性肝炎肝癌的诊断价值。结果HCV-RNA高载量组患者CEA、AFP水平均高于HCV-RNA低载量组,差异均有统计学意义(P﹤0.05)。HCV-RNA载量与CEA、AFP水平均呈正相关(r=0.321、0.284,P﹤0.05)。ROC曲线显示,CEA和AFP联合检测诊断HCV-RNA高载量丙型病毒性肝炎肝癌的AUC最大。结论HCV-RNA高载量丙型病毒性肝炎肝癌患者的CEA、AFP水平较高,且HCV-RNA载量与CEA、AFP水平呈正相关。CEA和AFP联合检测对HCV-RNA高载量丙型病毒性肝炎肝癌具有一定的诊断价值。

Biomarkers for the early diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.

PPP2R3A表达与乙型肝炎相关肝癌易感性及患者预后的关系

目的探讨PPP2R3A表达水平与乙型肝炎相关性肝癌易感性及患者预后的关系。方法选择2020年1月至2021年6月秦皇岛市第三医院收治的60例慢性乙型肝炎肝硬化患者(肝硬化组)和120例慢性乙型肝炎肝硬化癌变患者(肝癌组)作为研究对象。采用免疫组织化学染色法和ELISA法检测2组的病变肝组织和血清中PPP2R3A表达水平,分析肝癌组的血清PPP2R3A表达水平与患者临床病理特征的关系,以及肝癌组的病变肝组织中PPP2R3A表达与患者预后的关系。结果肝癌组病变肝组织中PPP2R3A高表达率显著高于肝硬化组(64.2%%比23.3%,P<0.05)。肝癌组的血清PPP2R3A表达水平显著高于肝硬化组[(14.05±4.68)ng/mL比(11.36±2.99)ng/mL,t=3.669,P<0.001]。肝癌组患者中,T2~T3期、血清DCP≥2000 ng/mL、AFP-L3%阳性和HBV-DNA表达阳性的患者的血清PPP2R3A表达水平分别较T1期、血清DCP<2000 ng/mL、AFP-L3%阴性和HBV-DNA表达阴性的患者显著升高(P均<0.05)。病变肝组织中PPP2R3A高表达组的1年总生存率显著低于低表达组(χ^(2)=4.546,P=0.033)。二分类Logistic回归分析结果显示,肝癌患者病变肝组织中PPP2R3A高表达、T2~T3期、AFP-L3%阳性及血清DCP水平升高均为患者预后的独立危险因素(P均<0.05)。结论PPP2R3A在肝癌患者血清和病变肝组织中均呈高表达,且与不良预后相关,是肝癌患者生存的独立危险因素,也是肝癌患者早期诊断和预后预测的潜在指标。

基于蛋白A/纳米金/壳聚糖分散的多壁碳纳米管修饰的电位型甲胎蛋白免疫传感器的研究

将壳聚糖分散的多壁碳纳米管（MWNT—CS）滴涂于金电极（Au）表面，利用壳聚糖大量的氨基将纳米金（nano-Au）固定到金电极表面，再利用蛋白A（PA）的定向固定效应将甲胎蛋白抗体（anti—AFP）固定到纳米金修饰的金电极表面，从而制得高灵敏、高稳定电位型甲胎蛋白免疫传感器。蛋白A为抗原和抗体的反应提供了合理的基础，纳米金的存在提高了抗体在电极表面的固定量，多壁碳纳米管（MWNT）促进了电子的传递，从而缩短电极的响应时问。在优化的实验条件下，该传感器响应的电极电位与甲胎蛋白浓度的对数在7．0～190．0μg/L的范围内保持良好的线性关系，检出限（S／N=3）为3．9μg/L.

甲胎蛋白变异体作为肝细胞癌预后指标的研究

目的探讨AFP变异体作为HCC预后指标的意义,为临床应用提供依据.方法本研究涉及1991～1994年在我院第一次行肝癌根治性切除术的AFP阳性HCC患者129例,术前采用小豌豆凝集素亲和免疫电泳自显影法测定血清AFP变异体含量,术后随访至1999年,将相关资料进行归纳整理,分析血清AFP变异体含量与HCC复发率、生存率的关系,并进行统计学分析.结果 129例HCC患者1,3,5年累计复发率分别为32.6%,66.7%和86.8%.AFP变异体含量≥20%组(A组,83例)和AFP变异体含量＜20%组(B组,46例)的累计复发率分别为37.3%和23.9%(1年),73.5%和54.3%(3年),92.8%和76.1%(5年).A组累计复发率明显增高(P＜0.05).129例HCC患者1,3,5年生存率分别为88.4%,63.6%和41.1%.A组和B组累计生存率分别为84.3%和95.7%(1年),56.7%和76.1%(3年),32.5%和56.5%(5年).B组生存时间明显延长(P＜0.01).结论AFP变异体是恶性生物学的良好指标,作为一个独立的预后标志物,可在临床上用于预测HCC预后和复发.

丝蛋白膜免疫传感器的研制及临床分析应用

报道了一种可用于临床测定甲胎蛋白的电化学免疫传感器．该传感器采用蚕丝蛋白膜作为固定甲胎蛋白抗体的载体，Ａｇ－ＡｇＣｌ电极作为换能器，直接电位法测定．研究了蚕丝蛋白膜的制备，蚕丝蛋白膜固定甲胎蛋白抗体的三种方法：盐酸活化法、叠氮法、重氮法，以及这些固定方法用于免疫传感器后的结果及比较．其中以盐酸活化法的效果最好，该传感器测定甲胎蛋白的最低检测浓度可达到５μｇ／Ｌ，标准曲线范围在１０～３００μｇ／Ｌ，相关系数为０．９９９７．丝蛋白膜免疫传感器具有灵敏度高、制备和操作简便、样品用量少、电极稳定等优点．在临床分析中，样品的结果与放射免疫法相符．

573例原发性肝癌病因及临床特点分析

目的 分析原发性肝癌（PLC）患者的临床特点,分析发病的相关致病因素。方法 选择2005年1月至2014年1月河北医科大学第三医院中西医结合肝病科经血清学、肝脏影像学检查明确诊断的PLC患者573例,回顾性分析发病年龄、性别、病因、家族史、个人史及临床特点。结果 PLC患者发病年龄为17～92（58.7±10.8）岁,其中79.4%于40～69岁发病,尤以50～69岁高发,占61.6%;男女之比为4.5：1;男性平均发病年龄为（57.4±10.3）岁,显著早于女性[（64.5±11）岁,P〈0.001）];慢性HBV、HCV感染及酒精为主要的致病因素,单纯HBV感染、HBV感染合并酒精性肝病（ALD）、HCV感染和ALD所致的PLC依次为317例（55.3%）、154例（26.9%）、38例（6.6%）和22例（3.8%）,其平均发病年龄依次为（58.6±10.6）岁、（54.3±8.4）岁、（67.0±7.8）岁和（58.4±11.4）岁,HBV感染合并ALD患者发病年龄显著低于其余各组（P〈0.001）;491例（85.7%）PLC患者存在肝硬化,100例（21.2%）有HBV感染家族史,仅53例（9.3%）有PLC家族史;在333例HBV感染相关性PLC患者中,240例（72.1%）血清HBV DNA阳性;血清HBs Ag、HBe Ab、HBc Ab阳性占57.4%;血清甲胎蛋白（AFP）升高者为394例（79.1%）,其中大于400μg/L者197例（39.4%）,7～400μg/L者196例（39.2%）,105例（21.2%）正常。结论 HBV感染为PLC患者发病的主要病因,在HBV感染基础上长期饮酒是促使PLC发病的主要危险因素,肝硬化为PLC发病的主要病理基础。肝癌家族史、糖尿病、吸烟亦为PLC发生的危险因素。AFP作为诊断PLC的主要血清标志,其诊断价值正在减弱。