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.

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.

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.

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.

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。

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.

首诊时伴血清甲胎蛋白升高胃癌的临床病理特点和预后分析

目的:探讨首诊时伴血清AFP升高的胃癌的临床病理特点及预后。方法:收集中国人民解放军联勤保障部队第904医院安徽医科大学无锡临床医学院2008年1月至2020年12月经胃镜活检首诊为胃腺癌的931例患者,以血清AFP≥20 ng/mL为标准筛选病例。H&E染色、免疫组织化学法和特殊染色明确病理学特点和免疫表型,并分析患者的临床特点和生存期。结果:931例胃腺癌中有36例(3.9%)首诊时出现血清AFP升高(20.7~6558.0 ng/mL)。患者无特异临床表现,影像学检查发现,36例患者中17例有远处转移,以肝转移最多见(13例),其余19例患者无远处转移。远处转移的病例其血清AFP水平明显高于无转移者(P=0.003)。病理分析显示,36例患者中16例为肝样腺癌,11例为伴有肠母细胞分化的腺癌,9例为普通腺癌。上述胃癌亚型均表达原始分化的标志物SALL4、GPC3、AFP。随访显示,无远处转移的19例患者的总生存期明显高于有远处转移的17例患者(P=0.002)。无远处转移的19例患者有16例进行了胃癌根治手术,其与经手术根治的AFP正常的314例普通胃癌相比,无病生存期更短(P=0.044),但总生存期差异无统计学意义(P=0.093)。结论:首诊时伴血清AFP升高的胃癌较罕见,其病理类型主要为肝样腺癌和伴有肠母细胞分化的腺癌。此类患者近一半在首诊时可见以肝脏为主的远处转移,有远处转移者预后极差,而无远处转移者手术治疗后预后较好,但相对于无AFP升高的胃癌预后仍可能较差。

慢性乙型肝炎、乙型肝炎肝硬化和原发性肝癌患者血清腺苷脱氨酶、α-L-岩藻糖苷酶和AFP-L3水平变化及其临床意义探讨

目的探讨慢性乙型肝炎(CHB)、乙型肝炎肝硬化(LC)和乙型肝炎相关性原发性肝癌(PLC)患者血清腺苷脱氨酶(ADA)、α-L-岩藻糖苷酶(AFU)和甲胎蛋白-L3(AFP-L3)水平变化及其临床意义。方法2020年1月~2022年4月我院诊治的CHB患者76例、LC患者31例和乙型肝炎相关性PLC患者29例,采用酶比色法检测血清ADA水平,采用速率法检测血清AFU水平,采用ELISA检测血清AFP-L3水平。对CHB患者常规行肝活检术。应用受试者工作特征曲线(ROC)分析血清指标诊断PLC的效能。结果46例G2~G4的CHB患者血清ADA、AFU和AFP-L3水平分别为(29.6±5.1)μ/L、(34.7±5.0)μ/L和(6.9±1.2)%,显著高于30例G0/G1的CHB患者【分别为(25.4±3.9)μ/L、(29.5±5.2)μ/L和(5.8±0.8)%,P<0.05】,55例S2~S4的CHB患者血清ADA、AFU和AFP-L3水平分别为(43.8±10.1)μ/L、(66.5±18.8)μ/L和(8.3±1.3)%,显著高于21例S0/S1的CHB患者【分别为(28.1±6.0)μ/L、(33.0±8.4)μ/L和(6.4±1.1)%,P<0.05】;PLC患者血清ADA、AFU和AFP-L3水平分别为(51.3±5.2)μ/L、(82.0±9.5)μ/L和(9.2±1.3)%,显著高于LC患者【分别为(38.1±4.6)μ/L、(51.8±5.1)μ/L和(7.8±1.1)%,P<0.05】或CHB患者【分别为(26.5±4.6)μ/L、(30.9±5.6)μ/L和(6.1±0.8)%,P<0.05】;分别以血清AFP-L3=7.9%、AFU=55.1μ/L和ADA=46.0μ/L为截断点,AFP-L3诊断PLC的AUC为0.857,其灵敏度为86.2%,特异度为88.8%,显著优于AFU(分别为0.752、79.3%和77.6%)或ADA(分别为0.722、75.8%和76.6%,P<0.05)。结论应用血清AFP-L3水平诊断乙型肝炎患者罹患PLC的效能显著高于血清ADA或AFU水平,值得临床进一步验证。

分泌超高血清甲胎蛋白的胃肝样腺癌1例

目的提高对胃肝样腺癌(HAS)的临床特点、病理特点、诊断及治疗的认识。方法回顾性分析2021年10月22日江苏省肿瘤医院收治的1例HAS病人的临床资料。结果男,70岁,以“发现胃小弯部腺癌1周”收入院。胃镜提示胃小弯侧巨大溃疡,肝区未见明显占位,甲胎蛋白(AFP)>1000μg/L,经胃病理切片免疫组化诊断为肝样腺癌,后经免疫联合化疗病人AFP降至157μg/L。结论HAS无特异的临床表现,胃镜及影像学出现胃部肿物、溃疡、淋巴结转移,同时出现无法解释的AFP异常升高,应该考虑HAS,做到早发现早治疗。

血清甲胎蛋白、α-L-岩藻糖苷酶、碱性磷酸酶、谷氨酰转肽酶、乳酸脱氢酶检测对肝癌的诊断价值

目的探究血清甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、乳酸脱氢酶(LDH)在肝癌中的诊断价值。方法回顾性分析2019年8月至2021年4月福建医科大学附属第二医院收治的88例肝脏病变患者的临床资料,将34例肝癌患者纳入肝癌组,另将54例肝脏良性病变者纳入良性肝病组。采集所有血液标本,检测血清AFP、AFU、ALP、GGT、LDH水平。比较两组患者各血清肿瘤标志物水平,以病理组织学检查结果作为“金标准”,分析各血清肿瘤标志物水平在肝癌中的诊断价值,另计算各血清肿瘤标志物与病理结果的一致性。结果肝癌组AFP、AFU、ALP、GGT、LDH水平均高于良性肝病组,差异有统计学意义(P<0.05)。各指标联合检测敏感度、特异度、准确度、阳性预测值及阴性预测值均高于其他单项检测结果,且AFP、LDH与病理结果的一致性不佳,Kappa值分别为0.370、0.032;AFU、ALP、GGT与病理结果一致性尚可,Kappa值分别为0.460、0.505、0.566;联合检测与病理结果一致性良好,Kappa值为0.928。结论各血清肿瘤标志物联合检测在肝癌鉴别诊断中具有较高的临床应用价值,依据各肿瘤标志物水平变化有助于评估患者病情严重程度,且联合检测与病理结果存在较高的一致性,可将其作为诊断肝癌的首选方法,值得推广应用。

血清7种微RNA单独或联合甲胎蛋白检测对肝细胞癌的诊断价值

目的 分析血清7种miRNA(7miRNAs,包括miRNA-122、miRNA-192、miRNA-21、miRNA-223、miRNA-26a、miRNA-27a和miRNA-801)单独或联合甲胎蛋白(AFP)检测对肝细胞癌(HCC)的诊断价值。方法 选择2021年1月至2021年6月我院收治的249例患者为研究对象,其中163例为确诊的HCC患者(HCC组)、86例为非HCC患者(非HCC组)。检测两组患者血清7miRNAs和AFP水平,根据临床既定标准(7miRNAs≥-0.5和/或AFP≥20 ng/mL为阳性)计算2个指标单独和联合检测诊断HCC的灵敏度、特异度、阳性预测值和阴性预测值。运用ROC曲线分析2个指标单独及联合检测对HCC的诊断价值。结果 在249例患者中,HCC组患者的7miRNAs和AFP水平均高于非HCC组患者,差异均有统计学意义(P均<0.01)。血清7miRNAs、AFP和两者联合检测诊断HCC的灵敏度分别为75.46%、57.06%和87.12%,特异度分别为74.42%、94.19%和69.77%,阳性预测值分别为84.83%、94.90%和84.52%,阴性预测值分别为61.54%、53.64%和74.07%,AUC分别为0.787、0.819和0.864。结论 血清7miRNAs和AFP联合检测对HCC的诊断效能优于AFP单独检测,有更高的诊断价值。

甲胎蛋白、糖类抗原19-9、癌胚抗原联合检测对恶性腹腔积液的诊断价值~

目的 探讨甲胎蛋白(AFP)、糖类抗原19-9(CA19-9)、癌胚抗原(CEA)联合检测对恶性腹腔积液的诊断价值。方法 根据腹腔积液性质的不同将103例腹腔积液患者分为对照组(n=50,良性腹腔积液)和观察组(n=53,恶性腹腔积液)。比较两组患者腹腔积液中AFP、CA19-9、CEA水平。以病理检查结果为金标准,分析AFP、CA19-9、CEA单独及联合检测对恶性腹腔积液的诊断价值,采用Kappa检验进行一致性分析。应用受试者工作特征(ROC)曲线及曲线下面积(AUC)评估AFP、CA19-9、CEA单独及联合检测对恶性腹腔积液的诊断价值。结果 观察组患者的AFP、CA19-9、CEA水平均明显高于对照组,差异均有统计学意义(P﹤0.01)。AFP、CA19-9、CEA联合检测诊断恶性腹腔积液的灵敏度、特异度、准确度分别为94.34%、96.00%、95.15%,均高于AFP、CA19-9、CEA单独检测。AFP、CA19-9、CEA单独及联合检测诊断恶性腹腔积液与病理检查的一致性Kappa值分别为0.43、0.56、0.53、0.92。ROC曲线显示,AFP、CA19-9、CEA联合检测诊断恶性腹腔积液的AUC为0.968,高于单独检测的0.794、0.827、0.816。结论 AFP、CA19-9、CEA联合检测对恶性腹腔积液具有较高的诊断价值,值得临床推广。

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.

血清AFP、AFU、ALP、GGT、LDH水平联合检测在肝癌诊断中的应用价值

目的:观察血清甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、乳酸脱氢酶(LDH)水平联合检测在肝癌诊断中的应用价值。方法:回顾性分析2019年8月至2021年4月88例疑似肝癌患者的临床资料,按病理学检查结果分为肝癌组34例和良性肝病组54例。另取同期40名健康体检者的临床资料,设为对照组。比较三组血清ALP、AFU、GGT、LDH和AFP水平,采用受试者工作特征(ROC)曲线分析AFP、AFU、ALP、GGT、LDH水平联合检测在肝癌鉴别诊断中的应用价值。结果:肝癌组、良性肝病组血清AFP、AFU、ALP、GGT、LDH水平均高于对照组,且肝癌组高于良性肝病组,差异有统计学意义(P<0.05);血清AFP、AFU、ALP、GGT、LDH水平联合检测诊断肝癌的曲线下面积(AUC)为0.976,高于各单项检测(AUC=0.835、0.777、0.882、0.907、0.802)。结论:血清AFP、AFU、ALP、GGT、LDH水平联合检测诊断肝癌的价值高于各单项检测诊断价值。