MTHFR基因多态性及血清AFP水平与胎儿神经管畸形的关系

目的分析亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血清甲胎蛋白(AFP)与胎儿神经管畸形的关系。方法选取2018年1月至2023年11月在陕西省宝鸡市妇幼保健院引产或分娩的50例胎儿神经管畸形产妇作为观察组,另选取150例胎儿健康产妇作为对照组。比较两组MTHFR基因多态性分布情况及血清AFP水平,比较观察组不同MTHFR基因多态性血清AFP水平,采用多因素Logistic回归分析胎儿神经管畸形的危险因素。结果观察组MTHFR C677T基因CT基因型+TT基因型、MTHFR A1298C基因AC基因型+CC基因型比例及血清AFP水平高于对照组,差异均有统计学意义(P<0.05)。观察组MTHFR C677T基因CT基因型+TT基因型产妇血清AFP水平高于CC基因型,MTHFR A1298C基因AC基因型+CC基因型产妇血清AFP水平高于AA基因型,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,MTHFR C677T基因CT基因型+TT基因型、MTHFR A1298C基因AC基因型+CC基因型是发生胎儿神经管畸形的危险因素(P<0.05)。结论MTHFR C677T基因、MTHFR A1298C基因多态性及血清AFP水平与胎儿神经管畸形有关,在预测胎儿神经管畸形方面有一定应用价值。

联合检测CHI3L1、AFP和GGT在乙肝相关肝癌患者中的相关性研究

目的探讨血清壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)、甲胎蛋白(alpha fetoprotein,AFP)和γ-谷氨酰转移酶(γ-glutamyl transferase,GGT)检测在乙型肝炎病毒(hepatitis B virus,HBV)感染相关肝癌诊断中的临床应用价值。方法选取2021年7月—2023年7月在玉林市第一人民医院就诊HBV病毒感染相关的50例肝癌患者,50例肝硬化患者,50例慢性乙型肝炎患者以及50名同期健康体检者作为研究对象。比较4组研究对象血清中CHI3L1、AFP、GGT、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)等水平的差异,用受试者工作特征(receiver operating characteristic curve,ROC)曲线评估各指标在肝癌中的诊断价值。结果肝炎组、肝硬化组、肝癌组的CHI3L1、AST、ALT水平均高于对照组,肝癌组AFP、GGT水平高于对照组,差异有统计学意义(P<0.05)。与肝炎组比较,肝硬化组及肝癌组的CHI3L1、AFP、GGT、AST、ALT水平均升高,差异有统计学意义(P<0.05)。与肝硬化组比较,肝癌组的CHI3L1、AFP、GGT、AST水平均升高,差异有统计学意义(P<0.05)。ROC曲线分析显示,CHI3L1、AFP、GGT联合时的曲线下面积(area under the curve,AUC)最大(AUC=0.936)。Spearman相关分析结果显示,CHI3L1与AST呈正相关(r=0.414,P=0.003),AFP与GGT呈正相关(r=0.437,P=0.002),AFP与AST呈正相关(r=0.504,P<0.001),GGT与AST呈正相关(r=0.759,P<0.001),GGT与ALT呈正相关(r=0.636,P<0.001)。结论CHI3L1、AFP及GGT联合检测可提高肝癌的诊断价值,对临床肝癌患者诊疗有重要作用。

血清lncRNA T342620联合AFP对肝癌的诊断价值

目的探究肝癌患者血清长链非编码RNA(lncRNA)T342620的表达水平,及其单独或联合甲胎蛋白(AFP)诊断肝癌的临床应用价值。方法采用病例对照研究,收集2021年4月至2023年5月在中国人民解放军南部战区总医院治疗的69例原发性肝癌患者(肝癌组)、32例乙型肝炎患者(乙肝组)、20例肝硬化患者(肝硬化组)、30例原发性肝癌经导管肝动脉化疗栓塞术(TACE)术后患者(肝癌术后组)和同期进行体检的50例健康者(健康体检组)的血清,提取血清总RNA,采用实时荧光定量PCR技术,检测血清中lncRNA T342620的相对表达量;结合患者临床诊疗资料,分析其表达水平与病理特征和血清学相关指标的相关性;运用受试者工作特征(ROC)曲线分析lncRNA T342620单独及联合AFP对肝癌诊断的特异度和灵敏度。根据ROC曲线下面积(AUC)判断诊断效能,评估其在肝癌诊断中的应用价值。各组间比较采用χ^(2)检验,相关性分析采用Spearman法。结果lncRNA T342620在肝癌组和肝癌术后组血清表达水平较健康体检组、乙肝组、肝硬化组高,差异均具有统计学意义(P<0.001);临床病理和血清学相关指标分析显示:肿瘤越大,血清lncRNAT342620表达水平越高,肝癌组血清lncRNA T342620表达水平与白蛋白(ALB)和白球比(A/G)呈负相关(P<0.05),与α-L-岩藻糖苷酶(AFU)和HBV-DNA呈正相关(P<0.05),肝癌术后组患者血清lncRNA T342620表达水平与总胆汁酸(TBA)呈正相关(P<0.05);ROC曲线分析显示:血清lncRNA T342620用于区别肝癌患者与健康者、乙肝和肝硬化患者时,其灵敏度和特异度分别为55.1%和94.1%,具有较好的诊断价值;和AFP联合检测时,灵敏度和特异度分别为91.3%和91.2%,其灵敏度高于各单项指标诊断的灵敏度,且联合检测诊断效能最高,AUC为0.954,与AFP和lncRNA-T342620单独检测的AUC(0.906、0.758)比较,差异有统计学意义(P<0.05)。结论血清lncRNA T342620有可能成为肝癌辅助诊断的新型血清分子标志物。

腹腔镜规则性肝叶切除术对原发性肝癌患者肝功能、免疫功能、血清AFP、Hcy水平的影响

目的:探究腹腔镜规则性肝叶切除术对原发性肝癌(PLC)患者肝功能、免疫功能、血清甲胎蛋白(AFP)、同型半胱氨酸(Hcy)水平的影响。方法:回顾性分析2019年1月—2023年6月于贵州省人民医院接受手术治疗的200例PLC患者的临床资料,将行开腹手术的100例患者纳入对照组,行腹腔镜规则性肝叶切除术的100例患者纳入观察组。观察两组术后肝功能[总胆红素(TBIL)、白蛋白(ALB)、丙氨酸转移酶(ALT)、天冬氨酸氨基转移酶(AST)]、免疫功能(CD8^(+)、CD4^(+)、CD3^(+))、炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)]及血清AFP、Hcy水平的变化情况。结果:术前,两组肝功能、免疫功能、炎症因子、血清AFP、Hcy水平比较,差异无统计学意义(P>0.05);术后1 d,两组ALB高于术前,TBIL、ALT、AST及术后5 d的AFP、Hcy均低于术前,且研究组ALB高于对照组,TBIL、ALT、AST、AFP、Hcy低于对照组,差异有统计学意义(P<0.05);术后5 d,对照组TNF-α、IL-6水平均高于术前,CD8^(+)、CD4^(+)、^(+)CD3水平均低于术前,差异有统计学意义(P<0.05),术后5 d,研究组TNF-α、IL-6水平均低于对照组,CD8^(+)、CD4^(+)、^(+)CD3水平均高于对照组,差异有统计学意义(P<0.05)。结论:PLC患者予以腹腔镜规则性肝叶切除术治疗可明显降低患者术后血清AFP、Hcy水平,降低炎症因子水平,提高免疫力,恢复肝功能。

Computed morphometric analysis and expression of alpha fetoprotein in hepatocellular carcinoma and its related lesion

INTRODUCTION Hepatocellular carcinoma(HCC)is closely relatedwith hepatitis and cirrhosis.In order to investigatethe pathogenesis and early pathologic diagnosis ofHCC,HCC and related lesions were analyzedqualitively and quantitively by automatic imageanalysor and immunohistochemical assay.

Clinical diagnosis and treatment of alpha-fetoprotein-negative small hepatic lesions

Objective： We examined 103 cases over the last five years and discussed diagnosis and treatment of alpha- fetoprotein （AFP）-negative small hepatic lesions. Background： Small hepatic lesions （less than 2 cm in diameter） usually have no typical imaging characteristics and therefore are difficult to diagnose, especially when AFP tests provide a negative result. Methods： A total of 103 patients with AFP-negative small hepatic lesions from January 2003 to December 2008 were retrospectively reviewed. Differential diagnosis was performed by digital subtraction angiography （DSA）, dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）, contrast-enhanced ultrasound （CEUS）, or positron emission tomography-computed tomography （PET-CT） based on the multiplicity of lesions. Ninety-four patients with suspected cancers underwent partial hepatectomy. Clinical data were collected from hospital records and follow-up questionnaires. Results： Hepatocellular carcinoma （HCC） diagnostic sensitivity of DSA, DCE-MRI, CEUS and PET-CT was 88.2%, 93.9%, 88.9% and 88.9%, respectively. The surgery-related complication rate was 6.4%. Prognosis was good, with 1- and 3-year survival rates of 98.8% and 76.1%, respectively. Conclusions： DSA, DCE-MRI, CEUS and PET-CT are valuable for diagnosis of small hepatic lesions. Partial hepatectomy is a preferred surgical procedure. Surgery for small liver cancers usually has little risk and good prognosis, therefore it can be actively applied in suspected HCC cases.

Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma

AIM:To investigate the biological role of alpha fetoprotein (AFP) and its clinical signif icance in carcinogenesis of hepatocellular carcinoma (HCC).METHODS:Clinical analysis of HCC patients and im-munohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy,Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide,Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism.RESULTS: Among the 160 HCC patients enrolled in this study,130 patients survived 2 years (81.25%),with a survival rate of 86.8% in AFP < 2 0 μg/L group,88.9% in AFP 20-250 μg/L group,and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was benef icial only in patients with low AFP levels.The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management.The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP.Consistently,in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth,and this was more apparent in HepG2 cells,in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percent-age of HepG2 cells in S phase after exposure to AFP was modestly increased.CONCLUSION:HCC patients with higher AFP levels show a higher mortality rate,which appears to be attributable to the growth promoting properties of AFP.

The relationship between second trimester alpha fetoprotein levels and adverse pregnancy outcome

Design: Retrospective analysis. Setting: East London Hospital. Subjects: 724 women who had maternal serum alphafetoprotein levels measured between 15 to 19 weeks gestation. Main outcome measure: The main outcome measures were defined as any case of preeclampsia, small-for-gestational age (SGA) birth- weight th centile, placental abruption, stillbirth or early neonatal death. Methods: Women with MSAFP > 2.0 Multiples of Median (MoM) were classified as screen positive. Results: 41 (5.7%) women developed preeclampsia. Women with MSAFP > 2.0 Multiples of the Median (MoM) were significantly more likely to develop preeclampsia (p th centile

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.

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.

血清AFP-L2与NIPT联合超声NT值在胎儿异常染色体筛查中的应用价值

目的探讨血清甲胎蛋白异质体L2(AFP-L2)、无创产前基因检测(NIPT)技术联合超声胎儿后颈部透明层的厚度(NT)值对24~28^(+6)胎儿染色体异常筛查的价值。方法选取2021年9月至2022年9月于医院接受早期孕检确认染色体异常的孕妇120例纳入染色体异常组,选取同期接受正常孕检且已完成胎儿染色体异常筛查的孕妇120名作为健康志愿者。对所有受检孕妇分别采取超声检查NT、血清AFP-L2检查、NIPT技术单独检测及三者联合检测。比较4种检测方式的阳性、阴性检出情况,以及4种检测方式对提高胎儿染色体异常筛查的诊断效能。结果与健康志愿者比较,染色体异常组胎儿AFP-L2检查水平较低,NT厚度较高(P<0.05)。与超声检查比较,血清AFP-L2检查、NIPT检查、联合检查阳性预测值、阴性预测值较高(P<0.05);与血清AFP-12检查比较,超声检查阳性预测值、阴性预测值较低,NIPT检查、联合检查阳性预测值、阴性预测值较高;与NIPT检查比较,血清AFP-12检查、超声检查阳性预测值、阴性预测值较低,联合检查阳性预测值、阴性预测值较高(P<0.05)。与超声检查比较,血清AFP-L2检查、NIPT检查、联合检查灵敏度、特异度和准确率较高(P<0.05);NIPT检查技术对于性染色体异常的总阳性预测值(PPV)为92.24%;对于54,X(含嵌合体)、54,XXX、54,XXY、54,XYY、性染色体微缺失微重复的PPV分别为49.05%、79.15%、85.55%、43.19%、57.69%。与血清AFP-12检查比较,超声检查灵敏度、特异度和准确率较低,NIPT检查、联合检查灵敏度、特异度和准确率较高,与NIPT检查比较,超声检查、血清AFP-12检查灵敏度、特异度和准确率较低,联合检查灵敏度、特异度和准确率较高(P<0.05)。结论通过超声检查、血清AFP-L2检查、NIPT技术对胎儿染色体不正常进行筛查,提高对胎儿染色体异常筛查的准确率,降低误诊率,具有良好的诊断效能。超声、血清AFP-L2检查联合NIPT技术对胎儿染色体异常筛查具有重要意义。

Prognostic role of alpha-fetoprotein response after hepatocellular carcinoma resection

AIM To investigate whether the change in pre-/post-operation serum alpha-fetoprotein(AFP) levels is a predictive factor for hepatocellular carcinoma(HCC) outcomes.METHODS We retrospectively analyzed 334 HCC patients who underwent hepatic resection at our hospital between January 2006 and December 2016. The patients were classified into three groups according to their change in serum AFP levels:(1) the normal group, pre-AFP ≤ 20 ng/m L and post-AFP ≤ 20 ng/m L;(2) the response group, pre-AFP > 20 ng/m L and post-AFP decrease of ≥ 50% of pre-AFP; and(3) the non-response group, pre-AFP level > 20 ng/m L and post-AFP decrease of < 50% or higher than pre-AFP level, or any pre-AFP level < 20 ng/m L but post-AFP >20 ng/m L RESULTS Univariate and multivariate analyses revealed thatmultiple tumors [hazard ratio(HR): 1.646, 95%CI: 1.15-2.35, P < 0.05], microvascular invasion(m VI)(HR: 1.573, 95%CI: 1.05-2.35, P < 0.05), and the nonresponse group(HR: 2.425, 95% CI: 1.42-4.13, P < 0.05) were significant independent risk factors for recurrencefree survival. Similarly, multiple tumors(HR: 1.99, 95%CI: 1.12-3.52, P < 0.05), m VI(HR: 3.24, 95%CI: 1.77-5.90, P < 0.05), and the non-response group(HR: 3.62, 95%CI: 1.59-8.21, P < 0.05) were also significant independent risk factors for overall survival. The nonresponse group had significantly lower overall survival rates and recurrence-free survival rates than both the normal group and the response group(P < 0.05). Thus, patients with no response regarding post-surgery AFP levels were associated with poor outcomes.CONCLUSION Serum AFP responses are significant prognostic factors for the surgical outcomes of HCC patients, suggesting post-resection AFP levels can direct the management of HCC patients.

Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma

AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P <0.001). Prolidase levels were significantly associated with tumor size and number(P < 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P < 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P< 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.

Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels

AIM To investigate the impact of alpha-fetoprotein(AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patient survival.METHODS Data of adult patients who received liver transplant(LT) for hepatocellular carcinoma(HCC) at our hospital from January 2000 to December 2013 were reviewed. Reviewed data included demographic characteristics, preoperative AFP level, operative details, follow-up details, and survival outcomes. Patients were mostly listed for LT based on Milan or UCSF criteria. For the purpose of this study, normal AFP level was defined as AFP value < 10 ng/m L, high AFP level was defined as AFP value ≥ 10 to < 400 ng/m L, and very highAFP level was defined as AFP ≥ 400 ng/m L. The patients were divided into these 3 groups accordingly. Survival rates were plotted as Kaplan-Meier curves and compared by log-rank analysis. Continuous variables were expressed as median(interquartile range). Categorical variables were compared by Spearman's test. Discriminative analysis was used to define the lowest value of AFP that could affect the overall survival in study population. Statistical significance was defined by a P value of < 0.05.RESULTS Totally 250 adult patients underwent LT for HCC in the study period. Eight-four of them received deceaseddonor LT and 166 had living-donor LT. The patients were divided into 3 groups: Group A, AFP < 10 ng/m L(n = 83); Group B, AFP ≥ 10 to < 400 ng/m L(n = 131); Group C, AFP ≥ 400 ng/m L(n = 36). The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar(median, 13 vs 13 vs 12; P = 0.745). The time to operation in Group A was longer(median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality(P = 0.626) and postoperative complication(P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, but the tumors in Group C were larger(A: 2.5 cm, B: 3.0 cm, C: 4.0 cm; P = 0.003). Group C had a bigger proportion of patients who were beyond Milan criteria(P = 0.010). Poor differentiation and vascular permeation were also more common in this group(P = 0.017 and P = 0.003 respectively). It also had poorer 5-year survival(A: 85.5%, B: 82.4%, C: 66%; P = 0.029). The 5-year disease-free survival was 84.3% in Group A, 80.1% in Group B, and 61.1% in Group C. Receiver operating characteristic area under the curve for AFP in predicting tumor recurrence was 0.685. The selected cut-off value was 54 ng/m L for AFP(C-index 0.685; 95%CI: 0.592-0.779; sensitivity 0.595; specificity 0.687). On discriminative analysis, AFP value of 105 ng/m L was shown to affect the overall survival of the patients.CONCLUSION HCC patients with a high preoperative AFP level had inferior survival after LT. AFP level of 54 ng/m L was associated with disease recurrence, and AFP level of 105 ng/m L was found to be the cut-off value for overall survival difference.

Alpha-fetoprotein specific CD4 and CD8 T cell responses in patients with hepatocellular carcinoma

The presence of CD8 T cell responses to tumor associated antigens have been reported in patients with different malignancies. However, there is very little inf ormation on a comparable CD8 and CD4 T cell response to a tumor antigen in liver cancer patients. Here, we re-examine the kinetic and the pattern of T helper 1 and cytotoxic T lymphocyte responses to alpha-fetoprotein (AFP),a tumor rejection antigen in hepatocellular carcinoma (HCC). Then, we discuss the possibility of using AFP-based immunotherapy in combination with necrotizing treatments in HCC patients.

Association between serum alpha-fetoprotein levels and fatty liver disease: A cross-sectional study

AIM: To investigate the association between serum alpha-fetoprotein (AFP) levels and fatty liver disease (FLD) in a Chinese population.

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.

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.

Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation

AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.

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.