热休克蛋白70在肝细胞癌中的表达及作用

热休克蛋白(HSP)70在肝细胞癌(HCC)组织中呈不同程度的表达,其表达及调节机制尚不清楚,能否为HCC的早期诊断、治疗及预后提供帮助成为学者们研究的热点。从HSP70来源及家族、在HCC中的异常表达、与HCC各种治疗方法及其预后相关性等方面进行了综述,旨在为HCC的临床诊断及治疗提供帮助。     

血清热休克蛋白90α对肝细胞癌经肝动脉化疗栓塞术后生存的预测价值

目的 探讨术前血清热休克蛋白90α（HSP90α）水平对经肝动脉化疗栓塞术（TACE）治疗的肝细胞癌患者术后生存时间的影响。方法 回顾性分析2019年1月1日—2020年6月1日于西南医科大学附属医院肝胆外科接受单一TACE治疗的97例肝细胞癌患者的临床资料。以患者血清HSP90α水平的中位数作为临界值,将入组病例分为高水平组（HSP90α>135 ng/L,n=48）和低水平组（HSP90α≤135 ng/L,n=49）。计数资料2组间的比较采用χ²检验。采用Kaplan-Meier法计算中位生存时间,组间比较采用log-rank检验。通过log-rank单因素分析及Cox回归多因素分析探索患者术后生存时间的影响因素。结果 血清HSP90α高水平组与低水平组患者的肝功能Child-Pugh分级（χ²=19.356,P<0.01）、肿瘤坏死（χ²=9.964,P=0.002）、BCLC分期（χ²=22.356,P<0.01）及ECOG评分（χ²=6.644,P...     

G-test在肝细胞癌筛查中的诊断价值

目的 提高肝细胞癌(hepatocellular carcinoma,HCC)患者的诊断对其生存率具有重要的意义.甲胎蛋白(alpha-fetoprotein,AFP)普遍应用于HCC的筛查与诊断,但是其敏感度和特异度存在不足,因此有必要进一步筛选相关标记物提高HCC的诊断率.方法 对临床诊断为HCC患者及考虑存在HC...     

血清甲胎蛋白和高尔基体糖蛋白73联合检测对肝细胞癌的早期诊断价值

目的探讨血清甲胎蛋白(AFP)和高尔基体糖蛋白73(GP73)联合检测对肝细胞癌(HCC)的诊断价值,为早期诊断和鉴别诊断HCC提供依据。方法收集2012年6月-2013年5月住院患者标本共408例,其中HCC患者142例(HCC组),慢性肝炎患者156例(慢性肝炎组),肝硬化患者110例(肝硬化组)。分别采用电化学发光法和酶联免疫吸附试验(ELISA)双抗体夹心法测定3组患者的血清AFP和GP73的浓度,检测结果组间比较采用方差分析,率的比较采用χ2检验。并使用MedCalc统计学软件计算2项指标联合检测对HCC诊断的敏感度和特异度。结果 HCC组血清AFP和GP73的浓度显著高于肝硬化组和慢性肝炎组,差异具有统计学意义(P0.05);肝硬化组血清AFP和GP73的浓度显著高于慢性肝炎组,其差异亦有统计学意义(P0.05)。二者联合检测肝细胞癌的敏感度为95.8%,特异度为98.6%,较单项检测差异具有统计学意义(P0.05)。结论血清AFP和GP73联合检测对HCC具有较高的诊断价值和临床意义,可作为HCC早期的诊断和鉴别诊断指标,值得在临床上推广。     

PIVKAⅡ在肝细胞癌诊断中的价值

目的:由于维生素K缺乏或拮抗产生的异常蛋白(PIVKAⅡ),又称为γ-羧基凝血素,是近年来在日本及美国诊断肝细胞癌(HCC)的敏感指标,但至今仍未用于中国临床。本研究的目的是评价PIVKAⅡ在中国肝癌患者诊断中的意义。方法:检测60例HCC和30例排除肝癌的肝硬化患者血清中PIVKAⅡ和甲胎球蛋白(AFP)水平。结果:在HCC患者中,血清PIVKAⅡ的浓度为784.3±1364.1,显著高于肝硬化患者的16.1±31.7(P<0.001)。当将PIVKAⅡ的临界值定为40mAU/ml时,51.7％肝癌患者(31/60)的PIVKAⅡ值高于该临界值(灵敏度);但仅13.3％肝硬化患者PIVKAⅡ值高于此临界值。该指标的特异性为86.7％(26/30);精确度为62.2％(31+26/60+30);其中36.84％的小HCC患者(7/19)的PIVKAⅡ值高于此临界值。在26例AFP阴性的肝癌患者中,有11例(46.2%)PIVKAⅡ值高于该临界值;肝癌患者的AFP和PIVKAⅡ水平未见显著相关(r=0.101,P=0.247)。PIVKAⅡ和AFP联合使用较AFP单独使用灵敏度升高21.6％,较PIVKAⅡ单独使用灵敏度升高26.7%;对小肝癌患者,则分别升高15.8％和21.1％。结论:PIVKAⅡ是对肝癌诊断的敏感指标,如果与AFP结合使用,其敏感性更高。     

甲胎蛋白应答在肝细胞癌治疗中的预后价值

肝细胞癌（HCC）是最常见的肝脏恶性肿瘤。因其恶性程度高、预后差,准确评估患者的治疗效果及预后情况至关重要。尽管目前影像学是肝癌预后评估的标准方法,但其仍存在诸多局限性。甲胎蛋白是重要的肝癌肿瘤标志物,广泛的应用于肝癌的筛查、诊断及预后评价。总结了甲胎蛋白应答在评判肝癌患者预后的相关文献。整体上,甲胎蛋白应答在肝癌患者接受射频消融、肝动脉化疗栓塞、钇90放射性栓塞、索拉菲尼等分子靶向药物、全身化疗、肝动脉灌注化疗或同步放化疗等治疗后具有良好的预后价值。     

高尔基蛋白73及联合甲胎蛋白对肝细胞癌诊断价值的Meta分析

目的：探讨GP73及联合AFP 对肝细胞癌的诊断价值。方法系统检索了 PubMed、Cochrane 图书馆、Embase、中国生物医学数据库,收集从2005年1至2013年1月所有关于GP73和AFP 对肝细胞癌（HCC）诊断的所有诊断性试验论文。按照纳入和排除标准选择文献、提取资料和评价纳入研究的方法学质量后,采用 Meta DiSc 1．4进行Meta分析。结果9个研究共纳入5884例患者,显示GP73对 HCC的敏感度和特异度分别为0．74（95％犆犐为0．72、0．77）和0．90（95％犆犐为0．89、0．91）,高于AFP的0．63（95％犆犐为0．60、0．65）和0．81（95％犆犐为0．80、0．83）,联合检测的敏感度可达0．86（95％犆犐为0．84、0．88）;GP73的SROC 曲线 Q＊值为0．7820,与AFP 的0．7553相比（Z＝0．49,P＝0．62＞0．05）无明显差异;两者联合的Q^＊值为0．8252,与AFP 相比（Z＝1．50,P＝0．13＞0．05）无明显差异。结论GP73对 HCC诊断的敏感度高于AFP,联合检测可提高诊断的敏感度,但联合检测及GP73对 HCC的综合诊断性能与AFP无差异。此进一步结论尚有待更高质量 Meta分析或者大样本,多中心、随机双盲试验来证实。     

热休克蛋白90在HBV复制中的作用

HBV传播范围广,慢性感染状态多,治愈率低,提高HBV治愈率有助于改善患者的长期预后状况。热休克蛋白90(Hsp90)是广泛存在于生物体内的一种分子伴侣蛋白。近年来越来越多的研究表明,Hsp90与HBV感染有关,在HBV的复制过程中起重要作用,可与病毒的特定蛋白相互作用促进病毒复制,也可与宿主自身蛋白相互作用来发挥功能。本文就近年来Hsp90在HBV复制中的作用相关研究进展作一综述,以期为以Hsp90为靶点的抗HBV药物研发与HBV防治提供新的理论指导和方向。     

血清高尔基体蛋白73诊断肝细胞癌价值探讨

目的评价血清高尔基体蛋白73（GP73）在肝细胞癌（HCC）诊断中的价值。方法选择400例HCC、100例肝硬化（LC）、100例慢性乙型肝炎（CHB）患者和200例健康对照者（HC）,分别采用ELISA和电化学发光法检测血清GP73和甲胎蛋白（AFP）水平;采用受试者工作特征曲线下面积（ AUROC）评估两者对HCC的诊断效能。结果 HCC、CHB和LC患者血清GP73水平分别为243.6±163.1ng/ml、85.6±35.3ng/ml和81.9±36.4ng/ml,均显著高于健康对照组（78.2±33.9ng/ml,P〈0.05）,但在CHB和LC组及HC三组间无统计学差异;GP73和AFP的最佳诊断临界值分别为150.7ng/ml和19.7ng/ml,GP73的AUROC为0.846,灵敏性为69.2%,特异度为90.5%,均显著优于AFP（AUROC为0.828,灵敏性为57.6%,特异度为88.1%,P〈0.05）;GP73与AFP两者联合检测可以进一步提高对HCC的诊断准确性（AUROC为0.887,灵敏性为73.5%,特异度为88.0%）;在AFP阴性与阳性的两组HCC患者中,GP73灵敏性和特异度无显著性差异。结论血清GP73对HCC的诊断效能高于AFP,两者联合检测可以进一步提高诊断效能。     

肝细胞癌早期诊断中的生物标志物

晚期肝细胞癌(HCC)患者预后通常较差,如若能早期诊断,并采取行之有效的治疗措施则可显著提高患者生存率。目前,AFP是检测HCC应用最广泛的血清标志物。然而,在一些HCC患者中并未发现AFP的升高。分析了AFP、乙型肝炎核心相关抗原、液体活检技术、微小RNA、长链非编码RNA及外泌体在HCC早期诊断中的应用潜力,通过探讨其研究进展,为HCC早期诊断方法的探索提供依据。     

甲胎蛋白异质体对诊断肝细胞癌的相关价值研究

目的评价甲胎蛋白异质体(AFP-L3)对于原发性肝癌(PHC)的诊断价值。方法收集本院2013年1月至2013年7月住院及门诊患者185例,包括PHC患者61例(PHC组)、肝硬化患者66例(肝硬化组)、慢性活动性肝炎患者58例(慢性肝炎组)。选择同期健康体检者60例为对照组。AFP-L3采用亲和吸附离心管分离血清,AFP和AFP-L3水平采用化学发光法检测,以AFP-L3≥10%为阳性诊断标准,计算AFP-L3的百分含量。结果 PHC组、肝硬化组、慢性肝炎组、对照组患者血清AFP-L3阳性率分别为78.02%、69.8%、78.26%、0%。PHC组患者AFP-L3水平与肝硬化组比较,差异无统计学意义(P=0.062)。PHC组患者AFP-L3水平与对照组比较,差异有统计学意义(P=0.031)。结论AFP-L3是国际公认的对PHC鉴别诊断的有用指标,但本研究显示其在良性肝病特别是肝硬化与PHC差别不明显,因此仍应与AFP及影像学联合检测更有利于PHC的诊断。     

Heat shock protein 70 chaperoned alpha-fetoprotein in human hepatocellular carcinoma cell line BEL-7402

AIM: To investigate the interaction between heat shock protein 70 (HSP70) and a-fetoprotein (AFP) in human hepatocellular carcinoma (HCC) cell line BEL-7402. METHODS: The expression and localization of HSP70 and AFP in human HCC cell line BEL-7402 were determined by immunocytochemistry and indirect immunofluorescence cytochemical staining. The interaction between HSP70 and AFP in HCC cells was analyzed by immunoprecipitation and Western blot. RESULTS: Immunocytochemical staining detection showed that HCC cell BEL-7402 expressed a high level of HSP70 and AFP synchronously. Both were stained in cell plasma. AFP existed in the immunoprecipitate of anti-HSP70 mAb, while there was HSP70 in the immunoprecipitate of anti-AFP mAb. CONCLUSION: HSP70 chaperones AFP in human HCC cell BEL-7402. The interaction between HSP70 and AFP in human HCC cell can be a new route to study the pathogenesis and immunotherapy of HCC.     

热休克蛋白-2基因多态性与肝细胞癌的相关性

肝细胞癌(HCC)是我国的常见恶性消化道肿瘤之一,全球发病率逐年升高,其发生和发展与遗传、免疫和环境等因素相关.热休克蛋白(HSP)70是生物细胞受到高温、感染、炎症和缺血等应激刺激时产生的一组在进化上高度保守的蛋白质,具有广泛的生物学功能,与HCC的发病关系密切.     

热休克蛋白gp96在原发性肝癌组织中的检测及其意义

热休克蛋白gp96的发现为肿瘤和病毒性肝炎等传染性疾病的免疫治疗开辟了新的途径。用免疫组织化学方法对gp96存原发性肝癌组织中的表达进行检测，探讨gp96在抗肝癌免疫反应中的作用。     

Diagnostic value of alpha-fetoprotein combined with neutrophil-to-lymphocyte ratio for hepatocellular carcinoma

Background

To investigate the diagnostic performance of alpha-fetoprotein (AFP) and neutrophil-to-lymphocyte ratio (NLR) as well as their combinations with other markers.

Methods

Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), AFP and levels as well as the numbers of neutrophils and lymphocytes of all enrolled patients were collected. The NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. Receiver operating characteristic (ROC) curve analysis was conducted to determine the ability of each marker and combination of markers to distinguish HCC and liver disease patients.

Results

In total, 545 patients were included in this study. The area under the ROC curve (AUC) values for AFP, ALT, AST, and NLR were 0.775 (0.738–0.810), 0.504 (0.461–0.547), 0.660 (0.618–0.699), and 0.738 (0.699–0.774) with optimal cut-off values of 24.6?ng/mL, 111?IU/mL, 27?IU/mL, and 2.979, respectively. Of the four biomarkers, AFP and NLR showed comparable specificity (0.881 and 0.858) and sensitivity (0.561 and 0.539). The combination of AFP and NLR showed the highest AUC (0.769) with a significantly higher sensitivity (0.767) and a lower specificity (0.773) compared to AFP or NLR alone, and it had the highest sum of sensitivity and specificity (1.54) among all combinations. In patients with AFP <?20?ng/mL, the NLR showed the highest AUC and combination with other markers did not improve the diagnostic accuracy.

Conclusions

Our data indicate that the combination of AFP and NLR offers better diagnostic performance than either marker alone for differentiating HCC from liver disease, which may benefit clinical screening.

     

Ultrasonography and alpha-fetoprotein in diagnosis of hepatocellular carcinoma in cirrhosis

The accuracy of ultrasound (US) and alpha-fetoprotein (AFP) in the diagnosis of hepatocellular carcinoma (HCC) in 363 patients with cirrhosis (C) and a clinical suspicion of HCC was assessed. The ultrasonographic patterns of HCC and their relationship with AFP values were analyzed. Echographic patterns were distributed as follows: 47 patients had sonodense lesions; 30 patients had hypoechoic lesions; 47 had mixed-pattern lesions, and in four patients focal dilated intrahepatic bile ducts were demonstrated. The sensitivity of US was 90%; specificity was 93.3%. Serum AFP level 500 ng/ml (RIA) was the first clue to the diagnosis in 71 patients (48.6%); specificity was 100%. In 28 patients AFP levels became significantly elevated during follow-up after US detection of HCC. No relationship between echo pattern and serum AFP levels was demonstrated. An algorithm for diagnosis of HCC is proposed.     

Serum alpha-fetoprotein in the early stage of human hepatocellular carcinoma

The serum alpha-fetoprotein levels of 17 patients with cancers less than or equal to 3 cm in size were studied using radioimmunoassay to determine alpha-fetoprotein response in the early stage of human hepatocellular carcinoma. The levels were normal in 6 patients (35%), and elevated to 645 +/- 1140 micrograms/L (mean +/- SD) in the remaining patients. The levels were not correlated with tumor size. In 10 surgically resected patients, 5 had elevated levels of alpha-fetoprotein that returned to normal after surgery. The levels and tumor sizes were serially observed for 3-26 mo in the remaining 7 patients not surgically treated. In 1 patient alpha-fetoprotein levels were persistently normal and in the other 6 patients, the levels tended to increase with a median doubling time of 60-75 days (range 30-223 days). Despite continued tumor growth, a spontaneous fall in serum alpha-fetoprotein levels was encountered in 4 patients; in 2 patients the levels even fell within the normal range. After this fall, the levels increased drastically in 4 patients. We concluded that in the early stage of hepatocellular carcinoma, serum alpha-fetoprotein level is frequently normal, and thus determination of serum alpha-fetoprotein levels only is not a reliable indicator in the early detection of human hepatocellular carcinoma. A spontaneous fall in the level of alpha-fetoprotein is not an uncommon finding in the early stages of this cancer and cannot be used to rule out the diagnosis of hepatocellular carcinoma.