The impact of alpha-fetoprotein(AFP),child-turcotte-pugh(CTP)score and disease staging on the survival of hepatocellular carcinoma(HCC)patients:a retrospective cohort from single oncology center

Background:Hepatocellular carcinoma(HCC)is the most common cause of cancer-related death in Saudi Arabia.Our study aimed to investigate the patterns of HCC and the effect of TNM staging,Alfa-fetoprotein(AFP),and Child-Turcotte Pugh(CTP)on patients’overall survival(OS).Methods:A retrospective analysis was conducted on 43 HCC patients at a single oncology center in Saudi Arabia from 2015 to 2020.All patients had to fulfill one of the following criteria:(a)a liver lesion reported as definitive HCC on dynamic imaging and/or(b)a biopsy-confirmed diagnosis.Results:The mean patient age of all HCC cases was 66.8 with a male-to-female ratio of 3.3:1.All patients were stratified into two groups:viral HCC(n=22,51%)and non-viral HCC(n=21,49%).Among viral-HCC patients,55%were due to HBV and 45%due to HCV.Cirrhosis was diagnosed in 79%of cases.Age and sex did not significantly statistically differ in OS among viral and non-viral HCC patients(p-value>0.05).About 65%of patients had tumor size>5 cm during the diagnosis,with a significant statistical difference in OS(p-value=0.027).AFP was>400 ng/ml in 45%of the patients.There was a statistically significant difference in the OS in terms of AFP levels(p-value=0.021).A statistically significant difference was also observed between the CTP score and OS(p-value=0.02).CTP class B had the longest survival.BSC was the most common treatment provided to HCC patients followed by sorafenib therapy.There was a significant statistical difference in OS among viral and non-viral HCC patients(p-value=0.008).Conclusions:The most common predictors for OS were the underlying cause of HCC,AFP,and tumor size.Being having non-viral etiology,a tumor size>5 cm,an AFP>400 ng/mL,and a CTP score class C were all negatively associated with OS.

Prognostic value of combined detection of alpha-fetoprotein,plasma prothrombin activity,and serum prealbumin in acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure(ACLF)is a liver disease based on chronic liver disease,which is significantly influenced by clinical treatment regimen and disease status,and despite the existence of multiple prognostic assessment indicators for ACLF,the overall sensitivity and accuracy are relatively low.AIM To investigate the prognostic value of the combined detection of alpha-fetoprotein(AFP),plasma prothrombin activity(PTA),and serum prealbumin(PA)in ACLF.METHODS This retrospective study included 87 patients with ACLF admitted from February 2021 to February 2023 and categorized them into the survival(n=47)and death(n=40)groups according to their clinical outcomes 3 months posttreatment.All the participants underwent AFP,PTA,and PA level measurements upon admission.Baseline data,as well as AFP,PTA,and PA levels,were comparatively analyzed.Pearson correlation coefficients were utilized to analyze the correlations of AFP,PTA,and PA with different survival outcomes in patients with ACLF.Receiver operating characteristic(ROC)curves and areas under the curves were used to evaluate the predictive value of AFP,PTA,and PA for ACLF prognosis.RESULTS AFP,PTA,and PA levels were markedly decreased in the death group than in the survival group(P<0.05).Pearson analysis indicated a positive association of the AFP,PTA,and PA levels with the survival of patients with ACLF(P<0.05).ROC curve analysis determined the sensitivity and specificity of the combined diagnosis at 91.24%and 100.00%,respectively,both of which were notably increased compared to the single-index diagnosis.The ROC of their combined diagnosis was 0.989,significantly surpassing 0.907,0.849,and 0.853 of AFP,PTA,and PA,respectively.No statistically significant variance was determined in the sensitivity and specificity of the combined diagnosis vs the single detection(P>0.05).CONCLUSION The combined detection of AFP,PTA,and PA levels demonstrates favorable diagnostic value for the short-term prognosis of patients with ACLF,featuring high sensitivity and specificity.

Inflammation-related markers and prognosis of alpha-fetoprotein producing gastric cancer

BACKGROUND Inflammation-related markers including neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),systemic immune-inflammation index(SII),systemic inflammation response index(SIRI)and prognostic nutritional index(PNI)could reflect tumor immune microenvironment and predict prognosis of cancers.However,it had not been explored in alpha-fetoprotein(AFP)producing gastric cancer(GC).AIM To determine the predictive value of inflammation-related peripheral blood markers including as NLR,PLR,MLR,SII,SIRI and PNI in the prognosis of AFPproducing GC(AFPGC).Besides,this study would also compare the differences in tumor immune microenvironment,clinical characteristics and prognosis between AFPGC and AFP-GC patients to improve the understanding of this disease.METHODS 573 patients enrolled were retrospectively studied.They were divided into AFP+group(AFP≥20 ng/mL)and AFP-group(AFP<20 ng/mL),comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis.In AFP+group,the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored.RESULTS Compared with AFP-patients,AFP+patients had higher NLR/PLR/MLR/SII/-SIRI and lower PNI levels and poorer overall survival(OS).In the AFP+group,mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group.Moreover,the dynamic increase(NLR/PLR/MLR/SII/-SIRI)or decrease(PNI)was associated with the rise of mortality within 1 year of follow-up.CONCLUSION Compared with AFP-patients,the level of inflammation-related peripheral blood markers significantly increased in AFP+patients,which was correlated with OS of AFP+patients.Also,the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+patients.AFPGC should be considered as a separate type and distinguished from AFP-GC because of the difference in tumor immune microenvironment.It requires basic experiments and large clinical samples in the future.

Des-gamma-carboxy prothrombin and alpha-fetoprotein levels as biomarkers for hepatocellular carcinoma and their correlation with radiological characteristics

BACKGROUND Alpha-fetoprotein(AFP),a commonly used biomarker for hepatocellular carcinoma(HCC),is normal in up to one-third of patients.AIM To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin(DCP)alone and in combination with AFP.METHODS In this study,202 patients with radiologically proven HCC were enrolled,and their DCP and AFP levels were evaluated for their diagnostic performance.RESULTS The mean age of the enrolled patients was 58.5 years;72.0%were male.DCP was elevated in 86.6%(n=175)of all patients,100.0%(n=74)of patients with portal vein thrombus,and 87.4%(n=111)of patients with multicentric HCC.AFP was elevated in 64.3%(n=130)of all the patients,74%(n=55)of the patients with portal vein thrombus,and 71.6%(n=91)of the patients with multicentric HCC(P=0.030,0.001,and 0.015,respectively).In tumors less than 2 cm in size(n=46),DCP was increased in 32(69.5%)patients,and AFP was increased in 25(54.3%)patients(P=0.801).There was good pairing between DCP and AFP for HCCs of 2 cm size or larger(P<0.001);however,the pairing among tumors<2 cm size was not significant(P=0.210).In 69 of the patients(34.1%),only one of the tumor markers was positive;DCP was elevated alone in 57/202(28.2%)of all patients,and AFP alone was elevated in 12/202(5.9%)of the patients.The areas under receiver operating characteristic curves(AUROC)for tumors>2 cm was 0.74 for DCP and 0.59 for AFP;combining both markers resulted in an AUROC of 0.73.For tumors<2 cm,the AUROC was 0.25 for DCP and 0.40 for AFP.CONCLUSION DCP,as an individual marker,had a better diagnostic performance in many cases of HCC.Hence,DCP may replace AFP as the primary HCC biomarker.

凝血功能5项联合甲胎蛋白在原发性肝癌诊断中的价值

目的分析凝血功能5项联合甲胎蛋白在原发性肝癌诊断中的价值。方法选2019年1月到2021年1月泰州市第四人民医院收治的原发性肝癌患者110例为研究组,另选取同期体检志愿者60例为对照组。检测两组凝血功能5项、甲胎蛋白水平。结果与对照组相比,研究组凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)较长,D-二聚体、甲胎蛋白(AFP)水平较高,纤维蛋白原(FIB)水平较低(P<0.05)。原发性肝癌Ⅰ~Ⅱ期、高分化、未发生淋巴结转移、肿瘤直径<4、单个结节、未出现静脉侵犯患者D-二聚体、TT、PT、APTT、AFP均低于Ⅲ~Ⅳ期、中低分化、淋巴结转移、肿瘤直径≧4、多发结节、出现静脉侵犯患者,FIB则相反(均P<0.05)。将性别、年龄等因素控制后,D-二聚体、TT、PT、APTT、AFP与临床分期、组织分化程度、淋巴结转移、肿瘤直径、肿瘤部位特点、静脉侵犯呈正相关,FIB与临床分期、组织分化程度、淋巴结转移、肿瘤直径、肿瘤部位特点、静脉侵犯呈负相关(P<0.05)。6项联合对原发性肝癌的诊断价值高于D-二聚体、TT、PT、APTT、FIB、AFP蛋白单项检测(P<0.05)。结论原发性肝癌患者TT、PT、APTT较长,D-二聚体、AFP水平较高,FIB水平较低,且D-二聚体、TT、PT、APTT、AFP表达情况与临床分期、组织分化程度、淋巴结转移、肿瘤直径、肿瘤部位特点、静脉侵犯相关,联合检测对原发性肝癌诊断价值较高。

纳米石墨适配体传感器结合酶信号放大检测甲胎蛋白

利用纳米石墨-适配体传感器结合脱氧核糖核酸酶(DNase I)信号放大策略检测了肿瘤标志物甲胎蛋白(AFP)。通过将纳米石墨(NG)和DNase I加入到适体(aptamer)溶液中合成了一种新型的荧光传感器NG/Aptamer。加入AFP后,AFP/aptamer复合物的形成导致aptamer从NG表面脱离,随后aptamer被DNase I分解,目标AFP被释放出来进行新一轮循环,从而实现了检测信号的明显放大。在最佳条件下,AFP浓度在3~150 pg·mL^(-1)范围内与荧光强度呈线性关系,检测限为2.556 pg·mL^(-1)。此外,所开发的传感器对AFP具有高度特异性,不会受到其他结构类似物质的干扰。该传感器也可应用于人血清样本中AFP的检测,回收率为95.1~103.8%。

诱骗受体3在肝癌临床诊疗中的研究进展

肝癌是一种严重的全球性疾病,其发病率和死亡率较高。诱骗受体3(DcR3)是一种肿瘤坏死因子超家族成员,其在多种肿瘤中表达异常。尤其在肝癌中,DcR3的表达水平显著高于正常肝组织,因此联合甲胎蛋白检测可作为一种早期诊断方法。DcR3也可以作为评估肝癌治疗效果的指标,其表达水平与疾病进程和患者预后密切相关。同时,DcR3的发现也为肝癌的靶向治疗提供了新靶点。通过抑制DcR3的表达或阻断其信号转导,抑制肝癌细胞的增殖和侵袭,为治疗肝癌提供了一种可能的新途径。未来通过深入研究DcR3的作用机制,开发针对DcR3的诊疗策略,有望为肝癌的个性化诊疗提供新的可能。

CA19-9、CEA、AFP检测联合128层MSCT对早期食管癌的诊断效果

目的 分析糖链抗原19-9(CA19-9)、癌胚抗原(Carcinoembryonic antigen,CEA)、甲胎蛋白(AFP)检测联合128层多层螺旋(CT(MSCT)对早期食管癌的诊断效果。方法 收集本院2021年6月至2023年10月收治的92例食管癌患者的临床资料(食管癌组)。另同期选取在本院进行健康体检的63例健康体检者作为对照组。观察食管癌大小、形态、密度等CT征象,比较不同人群CA19-9、CEA、AFP水平;并绘制受试者工作特征曲线(ROC),分析MSCT联合CA19-9、CEA、AFP对早期食管癌的诊断价值。结果 食管癌组CA19-9、CEA、AFP水平均明显高于对照组(P<0.05)。食管癌Ⅰ-Ⅱ期患者血清CA19-9、CEA、AFP1水平明显低于Ⅲ-Ⅳ期者(P<0.05)。ROC曲线示,MSCT、CA19-9、CEA、AFP四者联合检测曲线下面积(AUC)、敏感度、特异度分别为0.915、0.965、0.863,均高于各项指标单独检测。结论 CA19-9、CEA、AFP在食管癌中均呈高表达,可能与食管癌发生、发展有关;且上述因子联合MSCT检查可提高早期食管癌诊断价值。

血小板与淋巴细胞比值和甲胎蛋白对肝移植患者预后的预测价值

目的评估血小板与淋巴细胞比值(PLR)和甲胎蛋白(AFP)对肝移植患者预后的预测价值。方法选取2016年1月—2021年12月在宁波大学附属李惠利医院进行同种异体肝移植术的患者221例,收集其一般资料、相关检测指标及随访信息。利用受试者工作特征曲线计算曲线下面积(AUC)并获取最佳截断值,并根据最佳截断值将PLR和AFP分别分为高和低两组。采用Kaplan-Meier法绘制生存曲线,采用LogRank检验比较组间生存率的差异。采用Cox比例风险回归模型进行单因素和多因素分析。结果肝移植患者PLR和AFP的AUC分别为0.706、0.710(P<0.05)。高PLR组52例,1、3、5年生存率分别为96.2%、79.1%、69.0%;低PLR组169例,1、3、5年生存率分别为98.2%、94.2%、92.2%。高AFP组55例,1、3、5年生存率分别为94.5%、75.1%、69.2%;低AFP组166例,1、3、5年生存率分别为98.8%、95.2%、91.9%。单因素Cox回归分析显示,年龄、住院时间、肝癌、凝血酶原时间、Child-Turcotte-Pugh分级、PLR水平和AFP水平是肝移植患者预后的影响因素(P<0.05);多因素Cox回归分析显示,住院时间长、高PLR、高AFP是影响肝移植患者预后的独立危险因素(P<0.05)。结论住院时间长、高PLR、高AFP是影响肝移植患者预后的独立危险因素,临床上可将其作为简便、可行的预后评估工具。

MRI联合AFP-L3预测肝癌射频消融术后复发的研究

目的 本研究探讨血清凝集素反应性甲胎蛋白(serum lectin-reactive alpha-fetoprotein,AFP-L3)结合M RI预测经皮射频消融(radiofrequency ablation,RFA)后肝癌复发的价值。方法 纳入94例肝癌RFA患者和82名健康人。磁共振成像记录表观弥散系数(apparent diffusion Coefficient, ADC),定量测定所有受试者血清AFP-L3的浓度,分析其与治疗后临床疗效的相关性和预测作用。结果 肝癌患者血清AFP-L3水平高于健康对照组,ADC值低于健康对照组。肿瘤残留者的ADC值低于完全消融者,血清AFP-L3水平高于完全消融者,联合检测ADC值和血清AFP-L3水平诊断完全消融的敏感性和特异度分别为87.50%和87.18%,肿瘤结节数、肿瘤直径、AFP、AFP-L3和有无肝硬变均为肝癌术后1年内复发的独立危险因素。ADC值与血清AFP-L3水平联合检测对预测肝癌复发的敏感性为92.86%,特异性为69.62%。结论 ADC值与血清AFP-L3检测相结合,对射频治疗后肝癌的完全消融和复发有较好的预测作用。

立体定向放疗联合信迪利单抗和贝伐珠单抗治疗不可切除原发性肝癌的效果分析

目的探讨立体定向放疗联合信迪利单抗和贝伐珠单抗治疗不可切除肝癌的效果、安全性及预后指标。方法选取2022年3月—12月在中国人民解放军总医院第五医学中心放射治疗科接受立体定向放疗联合信迪利单抗和贝伐珠单抗类似物(双达方案)治疗的42例不可切除原发性肝癌患者,给予计划靶区处方剂量为36~50 Gy,分5~6次,连续照射,后序贯双达方案治疗,每3周为1个疗程,直至出现肿瘤进展或严重不良反应。采用Kaplan-Meier法计算总生存率和无进展生存率,并采用Log-rank检验进行比较;Cox比例风险模型分析影响预后的相关因素。结果中位随访时间为21.6个月,客观缓解率为69%,疾病控制率为85.7%,中位无进展生存期为10.0个月(95%CI:6.7~13.0),中位总生存期为23.3个月(95%CI:14.7~31.8)。不良反应多为1~2级,未发生致命性不良反应。治疗后6~8周AFP应答组中位总生存期显著优于AFP未应答组(未达到vs 11.8个月,P=0.007)。多因素分析显示AFP应答与患者良好的预后相关(HR=0.31,95%CI:0.13~0.75,P=0.009)。结论对于不可切除肝癌患者,立体定向放疗联合双达方案可改善患者生存且安全性可控,治疗后6~8周AFP水平下降>50%可作为潜在预后指标。

CRAFITY score and nomogram predict the clinical efficacy of lenvatinib combined with immune checkpoint inhibitors in hepatocellular carcinoma

BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.

核磁共振联合血清CK、AFP诊断对植入型凶险性前置胎盘应用子宫动脉栓塞术的价值分析

目的:探讨核磁共振联合血清CK、AFP诊断对植入型凶险性前置胎盘术前应用子宫动脉栓塞术的价值。方法:选取2022年1月至2023年12月本院收治的90例凶险性前置胎盘患者,按照术后病理学诊断结果分为胎盘植入组(48例)和非胎盘植入组(42例),比较两组患者血清CK、AFP水平,并结合核磁共振联合血清CK、AFP水平,分别采取针对性的手术方式。比较核磁共振、血清学诊断及两者联合诊断相关指标。另选同期以常规剖宫产术、病理学诊断为凶险性前置胎盘患者48例为对照组,比较植入组和对照组术后不良事件的发生率。结果:植入组患者血清CK、AFP水平明显高于非植入组(P<0.05);核磁共振联合血清检查对植入型凶险性前置胎盘的敏感度、准确度、阴性预测值均明显高于单独核磁共振或血清学检查(P<0.05);植入组患者术后不良事件发生率明显低于对照组(P<0.05)。结论:核磁共振联合血清CK、AFP检查对于植入型凶险性前置胎盘的诊断具有一定价值,可结合评估情况,决定是否应用术前子宫动脉栓塞术,术后不良事件发生率低。

The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells

AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS: The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722 x 10(-9)M (Bmax=12810 sites per cell) and 8.931 x 10(-8)M (Bmax=119700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION: The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.

Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice

AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.

Using receiver operating characteristic curves to evaluate the diagnostic value of the combination of multislice spiral CT and alpha-fetoprotein levels for small hepatocellular carcinoma in cirrhotic patients

BACKGROUND： The various combination of multiphase enhancement multislice spiral CT （MSCT） makes the diagno- sis of a small hepatocellular carcinoma （sHCC） on the back- ground of liver cirrhosis possible. This study was to explore whether the combination of MSCT enhancement scan and alpha-fetoprotein （AFP） level ficiency for sHCC. could increase the diagnostic ef- METHODS： This study included 35 sHCC patients and 52 cir- rhotic patients without image evidence of HCC as a control group. The diagnoses were made by three radiologists em- ploying a 5-point rating scale, with postoperative pathologic results as the gold standard. Receiver operating characteristic （ROC） curve analysis was performed to evaluate the diag- nostic value of the three MSCT combination modes （arterial phase＋portal-venous phase, arterial phase＋delayed phase, arterial phase＋portal-venous phase＋delayed phase） and AFP levels for sHCC on the background of liver cirrhosis. RESULTS： The area under ROC curve （AUC）, sensitivity, and specificity of the combination of arterial phase＋portal- venous phase＋delayed phase were 0.93, 93%, and 82%, respectively. The average AUC of the arterial phase＋portal- venous phase＋delayed phase combination was significantly greater than that of the arterial phase＋portal-venous phase （AUC=0.84, P=0.01） and arterial phase＋delayed phase （AUC=0.85, P=0.03）. Arterial phase＋portal-venous phase had a smaller AUC （0.84） than arterial phase＋delayed phase （0.85）, but the difference was insignificant （P=0.15）. After combining MSCT enhancement scan with AFP, the AUC, sensitivity, and specificity were 0.95, 94%, and 83%, respectively, indicating a greatly increased diagnostic efficiency for sHCC. CONCLUSIONS： The combination of AFP and 3 phases MSCT enhancement scan could increase the diagnostic efficiency for sHCC on the background of liver cirrhosis. The application of ROC curve analysis has provided a new method and reference in HCC diagnosis.

Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma

Alpha-fetoprotein(AFP)is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma(HCC)in combination with ultrasound and other imaging modalities.Its utility is limited because of both low sensitivity and specificity,and discrepancies among the different methods of measurements.Moreover,its accuracy varies according to patient characteristics and the AFP cut-off values used.Combination of AFP with novel biomarkers such as AFP-L3,Golgi specific membrane protein(GP73)and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC.Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis.Hereditary and other non-hepatic disorders can also cause AFP elevation.

Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.

Changes of serum alpha-fetoprotein and alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma: prognostic significance

BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long term follow-up were recorded and summarized. RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28% 57%, and 84%, and the overall survival rates were 86%, 61% and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 <10%; and group C: AFP-L3 >10%). Patients with positive postoperative AFP-L3had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative AFP-L3.CONCLUSION: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.