甲胎蛋白异质体在肝细胞癌中的诊断价值分析

目的:探讨甲胎蛋白异质体(AFP-L3)的检测对肝细胞肝癌(HCC)的诊断价值。方法:选取2009年2月至2012年11月在本院治疗的90例HCC患者为研究组,另选择同期接受治疗的慢性乙型肝炎患者30例和肝炎肝硬化患者30例作为对照组。观察三组患者的AFP、AFP-L3阳性率。结果:肝癌患者AFP和AFP-L3阳性率显著高于乙肝和肝硬化患者,差异具有统计学意义(P0.05)。乙肝和肝硬化两组患者的AFP及AFP-L3阳性率无显著差异(P0.05)。AFP400 ng/m L:肝癌组AFP-L3阳性率显著高于乙肝组和肝硬化组,差异具有统计学意义(P0.05)。结论:AFP-L3在HCC中的诊断价值较甲胎蛋白大,更适合在临床诊断中应用。     

原发性肝癌MRI检查图像特征分析及联合血清AFP、TK1、DKK1的诊断价值研究

摘要 目的：研究原发性肝癌（PHC）磁共振成像（MRI）检查图像特征及其联合血清甲胎蛋白（AFP）、胸苷激酶1（TK1）、Dickkopf相关蛋白1（DKK1）的诊断价值。方法：将我院从2017年1月～2020年1月收治的PHC患者76例纳入研究,记作观察组。另取同期我院收治的70例良性肝病患者记作对照组。对所有受试者均进行MRI扫描,比较两组MRI图像特征。检测并对比两组血清AFP、TK1、DKK1水平的差异。通过受试者工作特征（ROC）曲线分析MRI及上述各项血清学指标诊断PHC的效能。结果：PHC患者T1WI主要表现为均匀低或稍低信号,T2WI主要表现为不均匀高信号,DWI均表现为均匀高信号。观察组血清AFP、TK1、DKK1水平均高于对照组（均P＜0.05）。经ROC曲线分析可得：MRI检查联合血清AFP、TK1、DKK1诊断PHC的曲线下面积、灵敏度、特异度、准确度均高于上述各项检查方式单独诊断。结论：PHC患者MRI图像特征如下：T1WI主要表现为均匀低或稍低信号,T2WI主要表现为不均匀高信号,DWI均表现为均匀高信号。此外,MRI检查联合血清AFP、TK1、DKK1诊断PHC的效能较高,具有一定的临床应用价值。     

AFU, AFP, GP73和GPC3联合检测对原发性肝癌的诊断价值

目的:研究α-L-岩藻糖苷酶(AFU)、甲种胎儿球蛋白(AFP)、高尔基体蛋白73(GP73)和磷脂酰肌醇蛋白聚糖3(GPC3)联合检测对原发性肝癌的诊断价值。方法:选择2014年1月~2016年5月在我院进行诊治的原发性肝癌患者90例为肝癌组,同期住院诊治的肝硬化患者60例为肝硬化组,以及同期在我院体检健康者60例为对照组。比较三组的AFU、AFP、GP73和GPC3水平和阳性检出率,并观察AFU、AFP、GP73和GPC3单独检测和联合检测对原发性肝癌的诊断效率。结果:肝癌组和肝硬化组的AFU、AFP、GP73和GPC3水平均明显高于对照组(P0.05),且肝癌组明显高于肝硬化组(P0.05);肝癌组和肝硬化组的AFU、AFP、GP73和GPC3阳性率均明显高于对照组(P0.05),且肝癌组明显高于肝硬化组(P0.05);AFU、AFP、GP73和GPC3联合检测对原发性肝癌的特异性、敏感性、阳性预测值及阴性预测值均明显高于单独检测和三项指标联合检测(P0.05)。结论:AFU、AFP、GP73和GPC3联合检测可以提高对原发性肝癌的检出率,具有较高的临床应用价值。     

复方苦参注射液联合TACE对中晚期肝癌患者预后、生存质量和血清AFP、AFP-L3水平的影响

摘要 目的：观察肝动脉化疗栓塞术（TACE）联合复方苦参注射液对中晚期肝癌患者预后、生存质量和血清甲胎蛋白（AFP）、甲胎蛋白异质体（AFP-L3）水平的影响。方法：选择我院于2016年3月~2019年10月期间收治的98例中晚期肝癌患者,经随机数字表法分为对照组（49例,TACE治疗）和研究组（49例,复方苦参注射液联合TACE治疗）。对比两组疗效、生存率、生存质量改善率、血清AFP、AFP-L3水平及不良反应发生率。结果：与对照组比较,研究组的临床总有效率明显升高（P<0.05）。研究组的1年生存率高于对照组（P<0.05）。与对照组比较,研究组的生存质量改善率明显升高（P<0.05）。两组治疗后血清AFP、AFP-L3水平较治疗前下降,且研究组低于对照组（P<0.05）。两组不良反应总发生率组间对比无统计学差异（P>0.05）。结论：TACE基础上联合复方苦参注射液治疗中晚期肝癌患者,可改善其短期预后及生存质量,降低其血清AFP、AFP-L3水平。     

血清AFP,CEA,CA125单独或联合检测对原发性肝癌早期诊断的临床价值研究

目的:探讨血清中甲胎蛋白(AFP)、癌胚抗原(CEA)、糖类抗原125(CA125)单独以及联合检测对于原发性肝癌的早期诊断临床价值。方法:选择2012年1月~2016年6月在我院检验科确诊的120例原发性肝癌患者作为观察组,并以80例健康志愿者作为对照组,检测和比较两组的AFP、CEA和CA125水平,分析血清AFP、CEA、CA125单项及联合检测检出原发性肝癌的阳性率和约登指数。结果:观察组血清AFP(319.53±35.78 ng/mL)、CEA(81.4±27.8 ng/mL)、CA125(20.67±4.61 ng/mL)水平均明显高于健康对照组(P0.05)。血清AFP、CEA、CA125在单独检测时诊断原发性肝癌的敏感性分别为65%(78/120)、75%(90/120)和60%(72/120),而三者的联合检测能够使检测的敏感性达到92%(112/120),显著高于单独检测时的敏感度(P0.05)。血清AFP、CEA、CA125单项检测约登指数均显著低于联合检测(P0.05)。结论:相较于血清AFP、CEA、CA125的单独检测,三者联合检测可明显提高原发性肝癌的检出率。     

血清GP73联合Dickkopf-1、AFP对肝细胞癌的诊断价值

目的:探讨血清高尔基体蛋白(GP73)联合Dickkopf-1、甲胎蛋白(AFP)对肝细胞癌的诊断价值。方法:收集2014年9月至2016年9月我院收治的117例肝细胞癌患者(肝细胞癌组)、80例乙型病毒性肝炎患者(肝炎组),以及随机选取的80例健康体检者(对照组)为研究对象,采用酶联免疫吸附法(ELISA)测定各组对象的血清GP73、Dickkopf-1、AFP水平,并分析其与临床病理特征之间的关系,分析GP73、Dickkopf-1、AFP联合对肝细胞癌的诊断价值。结果:肝细胞癌组血清GP73、Dickkopf-1、AFP水平高于肝炎组、对照组,且肝炎组血清AFP水平高于对照组,差异有统计学意义(P0.05)。Child Pugh分级中B~C级肝细胞癌患者GP73、Dickkopf-1、AFP水平高于A级,差异有统计学意义(P0.05),不同分化程度、肿瘤直径、肿瘤数目患者的GP73、Dickkopf-1、AFP水平差异无统计学意义(P0.05)。GP73+Dickkopf-1+AFP对肝细胞癌诊断的灵敏度、特异性、阳性预测值、阴性预测值、准确率均高于GP73、Dickkopf-1、AFP的诊断结果,差异有统计学意义(P0.05)。结论:血清GP73、Dickkopf-1、AFP在肝细胞癌中呈高表达水平,三者联合可明显提高对肝细胞癌的诊断价值,临床有重要的参考价值。     

高尔基体蛋白73与肝癌诊断

肝癌是我国最常见的恶性肿瘤之一,血清甲胎蛋白(α-fetoprotein,AFP)检查是目前肝癌诊断最常采用的手段,但血清AFP对肝癌诊断的灵敏度和特异性均不理想,因此,临床上迫切需要更理想的肝癌标志物。高尔基体蛋白73(Golgi protein 73,GP73)是一种II型高尔基体跨膜糖蛋白,与肝炎、肝硬化和肝癌等肝病的发生、发展密切相关,GP73对肝癌诊断的灵敏度和特异性为65%和90%,而核心岩藻糖化GP73对肝癌诊断的灵敏度和特异性则高达90%和100%。GP73有可能成为一种更理想的肝癌临床诊断标志物,而核心岩藻糖化的GP73在肝癌的早期诊断中可能具有更重要的意义。     

磁共振扩散加权成像联合血清AFP、CA125、CEA、CA199检测在早期原发性肝癌中的诊断价值研究

摘要 目的：研究磁共振扩散加权成像（DWI）联合血清甲胎蛋白（AFP）、糖类抗原125（CA125）、癌胚抗原（CEA）、糖类抗原199（CA199）检测在早期原发性肝癌（PHC）中的诊断价值。方法：选取我院自2017年9月开始至2020年5月收治的63例早期PHC患者纳入研究,记作肝癌组,再取同期我院收治的61例良性肝病患者记作对照组。对所有受试者均实施DWI扫描,比较两组DWI图像信号强度。检测并比较两组血清AFP、CA125、CEA、CA199水平,以受试者工作特征（ROC）曲线分析上述各项血清学指标水平检测和DWI诊断早期PHC的效能。另外,比较PHC淋巴结转移患者和无淋巴结转移患者血清AFP、CA125、CEA、CA199水平。结果：肝癌组DWI信号强度为高信号人数占比高于对照组（均P<0.05）。肝癌组血清AFP、CA125、CEA、CA199水平均高于对照组（均P<0.05）。血清AFP、CA125、CEA、CA199水平联合DWI诊断早期PHC的曲线下面积、灵敏度以及特异度均高于上述各检查方式单独检测。PHC淋巴结转移患者的血清AFP、CA125、CEA、CA199水平均高于无淋巴结转移患者（均P<0.05）。结论：DWI联合血清AFP、CA125、CEA、CA199检测诊断早期PHC的价值较高,且淋巴结转移患者的血清AFP、CA125、CEA、CA199水平明显升高。     

腹部超声联合血清甲胎蛋白、高尔基体蛋白73、γ-谷氨酰转肽酶/血小板比值对慢性乙型肝炎患者肝纤维化的诊断价值研究

摘要 目的：探讨腹部超声联合血清甲胎蛋白（AFP）、高尔基体蛋白73（GP73）、γ-谷氨酰转肽酶/血小板比值（GPR）对慢性乙型肝炎患者肝纤维化的诊断价值。方法：选择新疆维吾尔自治区中医医院2020年3月～2022年2月期间收治的慢性乙型肝炎患者148例,根据肝脏活检病理诊断结果分为无肝纤维化组39例、轻度肝纤维化组33例、中度肝纤维化组51例、重度肝纤维化组25例。比较各组患者入院后腹部超声检查结果及血清AFP、GP73、GPR,应用受试者工作特征（ROC）曲线分析腹部超声联合AFP、GP73、GPR对慢性乙型肝炎患者肝纤维化的诊断价值。结果：随着肝纤维化程度地增加,患者肝脏轮廓逐渐不清晰、表面不光滑、肝脏回声逐渐增粗增强、有结节感、肝内胆管走形逐渐模糊,脂肪肝和腹水比例逐渐增加,脾脏厚度、脾脏长度、门静脉内径、脾静脉内径逐渐增加,经单因素方差分析显示各组超声指标比较差异有统计学意义（P<0.05）。腹部超声对慢性乙型肝炎患者肝纤维化诊断的灵敏度为79.82%、特异度为76.92%、准确度为79.05%。随着肝纤维化程度的增加,患者血清AFP、GP73及GPR逐渐增加,差异均有统计学意义（P<0.05）。ROC曲线分析结果显示,血清AFP、GP73、GPR对慢性乙型肝炎患者肝纤维化诊断具有较高的曲线下面积（AUC）,分别为0.701、0.664、0.779,腹部超声联合血清AFP、GP73、GPR对慢性乙型肝炎患者肝纤维化诊断的AUC最高（AUC为0.819）。结论：慢性乙型肝炎肝纤维化患者血清AFP、GP73、GPR升高,腹部超声联合血清AFP、GP73、GPR对慢性乙型肝炎患者肝纤维化具有较高的诊断价值。     

甲胎蛋白异质体在原发性肝癌患者血清中的表达

为了揭示原发性肝癌患者血清中甲胎蛋白异质体(AFP-L3)的表达及意义,本研究选取2014年2月至2016年3月在本院治疗的原发性肝癌患者80例,同时选取肝硬化患者60例,慢性乙肝患者60例及健康志愿者60例,采用亲和吸附离心管法检测不同受试者血清中AFP-L3水平。研究显示,原发性肝癌患者的血清AFP-L3 (122.13 ng/mL)水平显著低于肝硬化患者,并且显著高于慢性乙肝患者和健康者,差异具有统计学意义(p0.05);原发性肝癌患者中,血清AFP-L3水平在肿瘤大小≤3 cm (171.14 ng/mL)和TNM分期为Ⅰ～Ⅱ期(147.53 ng/mL)患者中显著高于肿瘤大小3 cm和TNM分期为Ⅲ～Ⅳ期患者(p0.05);血清AFP-L3高表达(≥122.13 ng/mL)的肝癌患者中位生存时间(22.76月)与血清AFP-L3低表达的肝癌患者(122.13 ng/mL)(22.04月)差异不显著(p0.05)。本项研究表明原发性肝癌患者血清中AFP-L3水平明显上升,并且与患者的肿瘤大小和TNM分期具有相关性。     

肝硬化原发性肝癌直径<1 cm超声造影表现及其与血清AFU、AFP-L3、GPC3、TSGF、GP73水平相关性研究

摘要 目的：探讨肝硬化原发性肝癌（PHC）直径<1cm超声造影（CEUS）表现及其与血清α-L-岩藻糖苷酶（AFU）、甲胎蛋白异质体-L3（AFP-L3）、磷脂酰肌醇蛋白聚糖-3（GPC3）、肿瘤特异生长因子（TSGF）、高尔基体糖蛋白（GP73）水平相关性。方法：选取2018年1月-2022年8月于湖北省襄阳市中医院收治的肝硬化PHC直径<1 cm患者44例,根据术后病理结果分为高分化组、中分化组和低分化组。所有患者术前均完善CEUS和血清AFU、AFP-L3、GPC3、TSGF、GP73水平检查。比较三组CEUS表现、定量时间-强度曲线（TIC）分析、血清AFU、AFP-L3、GPC3、TSGF、GP73水平。采用Spearman相关性分析肝硬化PHC直径<1 cm患者的CEUS表现与血清AFU、AFP-L3、GPC3、TSGF、GP73水平的相关性。结果：44例肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。不同分化程度肝硬化PHC直径<1 cm患者在动脉期、门脉期和延迟期的CEUS表现上差异均无统计学意义（P＞0.05）。高分化组、中分化组和低分化组的达峰时间、廓清时间和峰值加速时间逐渐减少,差异有统计学意义（P＜0.05）。而高分化组、中分化组和低分化组的峰值强度增加率逐渐增加,差异有统计学意义（P＜0.05）。高分化组、中分化组和低分化组的增强时间对比差异无统计学意义（P＞0.05）。高分化组、中分化组和低分化组血清AFU、AFP-L3、GPC3、TSGF、GP73水平逐渐升高,差异有统计学意义（P＜0.05）。Spearman相关性分析显示,达峰时间、廓清时间和峰值加速时间与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈负相关（P＜0.05）;峰值强度增加率与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈正相关（P＜0.05）。结论：肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。CEUS表现和血清AFU、AFP-L3、GPC3、TSGF、GP73水平具有相关性,两者可辅助鉴别肝硬化PHC直径<1 cm的不同分化程度。     

Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology-proven hepatocellular carcinoma

INTRODUCTION: Serum alpha-fetoprotein (AFP) is a useful marker of hepatocellular carcinoma (HCC), although the serum AFP concentration is also increased in patients with chronic liver diseases (CLD). The analysis of AFP glycoforms has been known to be of diagnostic value. We applied the lectin-affinity electrophoresis and antibody-affinity blotting techniques to HCC patients in Vietnam in order to better understand the role of lentil lectin-affinity AFP-L3 in the diagnosis and differential diagnosis of HCC, and its relationship with the biological characteristics of HCC. METHODS: Lens culinaris agglutinin-reactive AFP (AFP-L3) was measured in 65 patients with histologically proven HCC and 25 patients with CLD. All patients had serum AFP levels above 54 ng/mL. AFP-L3 levels were determined by lectin affinity electrophoresis coupled with antibody-affinity blotting. The diagnosis of HCC was confirmed histologically by ultrasound-guided biopsy. RESULTS: The mean value of AFP-L3 in the HCC patients was 49.6 +/- 21.6%, which was significantly higher (p<0.001) than that in the 25 CLD patients (10.7 +/- 4.3%). When the cutoff level for AFP-L3 was set at 15% (mean +/- SD), the sensitivity was 96.9%, the specificity 92.0% and the accuracy 95.5% in the 65 HCC patients. There was no clear correlation between serum AFP level and AFP-L3 percentage (r=0.16). There was no correlation between AFP-L3 and the maximum diameter of HCC nodules (r=0.05). However, the mean AFP-L3 value was higher in moderately or poorly differentiated HCC than in well differentiated tumors (p<0.001). CONCLUSIONS: AFP-L3 is potentially a clinically useful marker for the differentiation of increased AFP levels in hepatocellular carcinoma and chronic liver diseases. The AFP-L3 percentage is closely related to HCC differentiation. We consider the analysis of AFP-L3 a useful adjunct in the diagnosis of HCC.     

The Predictive Value of Golgi Protein 73 in Differentiating Benign from Malignant Liver Tumors

Introduction

In the work up of primary solid liver lesions it is essential to differentiate correctly between benign and malignant tumors, such as hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) respectively. A promising new marker to detect HCC is Golgi Protein 73 (GP73). Studies comparing patients with HCC and cirrhosis with normal controls suggested that GP73 is specific for patients with HCC; however, patients with other liver tumors were not included. We therefore studied the predictive value of GP73 in differentiating between solid benign and malignant liver tumors.

Materials and Methods

This study included 264 patients: 88 patients with HCC, 88 with hepatocellular adenoma (HCA), and 88 with focal nodal hyperplasia (FNH). A blood sample was collected from each patient to measure GP73 levels using a quantitative ELISA assay and differences in outcome between subgroups were compared. The receiver operating characteristic (ROC) curve, sensitivity and specificity of GP73 were calculated and compared to alpha-fetoprotein (AFP) levels.

Results

When comparing malignant and benign liver tumors the area under ROC was 0.701 and 0.912 for GP73 and AFP respectively. Test characteristics revealed a sensitivity of 60% for GP73 and 65% for AFP; in addition the specificity was 77% for GP73 and 96% for AFP.

Conclusion

Although the literature suggests that GP73 is a valuable serum marker in patients with HCC, the serum concentration may also be increased in patients with solid benign liver tumors. Therefore, a GP73 assay is less suitable for discriminating between primary malignant and benign tumors of the liver.     

Diagnostic Value of the Combination of Golgi Protein 73 and Alpha-Fetoprotein in Hepatocellular Carcinoma: A Meta-Analysis

Conflicting results have been widely reported on the use of Golgi protein 73 (GP73) as a serum biomarker for diagnosing hepatocellular carcinoma (HCC). This study evaluated the accuracy of GP73, alpha-fetoprotein (AFP), and GP73 + AFP for diagnosing HCC. The meta-analysis was performed on 11 studies that were selected by means of a comprehensive systematic literature review. Summary diagnostic accuracy, meta-regression analysis for heterogeneity and publication bias, and other statistical analyses were performed using Meta-Disc (version 1.4) and Stata (version 12.0). Pooled sensitivity, specificity, and diagnostic odds ratio were 0.77 (95% CI: 0.75–0.79), 0.91 (95% CI: 0.90–0.92), and 12.49 (95% CI: 4.91–31.79) for GP73; 0.62 (95% CI: 0.60–0.64), 0.84 (95% CI: 0.83–0.85), and 11.61 (95% CI: 8.02–16.81) for AFP; and 0.87 (95% CI: 0.85–0.89), 0.85 (95% CI: 0.84–0.86), and 30.63 (95% CI: 18.10–51.84) for GP73 + AFP. The area under the curve values were 0.86, 0.84, and 0.91 for GP73, AFP, and GP73 + AFP, respectively. These results indicate that for HCC diagnosis, the accuracy of GP73 was higher than that of AFP, and that GP73 + AFP exhibited significantly higher diagnostic accuracy than did GP73 or AFP alone.     

Evaluation of circulating Transforming growth factor-beta1, Glypican-3 and Golgi protein-73 mRNAs expression as predictive markers for hepatocellular carcinoma in Egyptian patients

Hepatocellular carcinoma (HCC) incidence is fast-growing especially in countries highly prevalent with viral hepatitis. Its poor prognosis has driven the research toward the discovery of sensitive markers for early detection. We investigated the usefulness of serum Transforming growth factor-beta1 (TGF-β1), Glypican-3 (GPC3), and Golgi protein-73 (GP73) mRNAs as early biomarkers in HCC Egyptian patients chronically infected with hepatitis C virus (HCV) in comparison with serum alpha-fetoprotein (AFP). Using semi-quantitative RT-PCR and densitometry analysis, circulating TGF-β1, GPC3, and GP73 mRNAs expressions were estimated in 15 healthy adults, 15 chronic HCV (CHC) patients and 25 HCC patients. Serum GP73 expression percentage in HCC group was significantly higher than controls (100 vs. 40 %, P ≤ 0.001) and when compared to elevated serum AFP levels (100 vs. 36 %, P ≤ 0.001). TGF-β1 and GP73 expression means were also higher in HCC patients than controls and CHC patients (P < 0.05). GPC3 expression showed higher frequency in CHC patients compared to HCC group (80 vs. 28 %, P = 0.0016). According to the study cutoffs, serum TGF-β1 and GP73 mRNAs showed 60 and 96 % sensitivities for HCC diagnosis with 100 and 95 % specificities, respectively. Furthermore, elevated GP73 mRNA expression levels in early HCC were significantly increased compared to those of TGF-β1 mRNA and to high serum AFP (92.3 vs. 53.8 and 23.1 %; P = 0.03 and 0.0004, respectively). In conclusion, circulating TGF-β1 and GP73 mRNAs could be useful biomarkers for HCV-induced HCC diagnosis. Moreover, serum GP73 mRNA is sensitive for early cancer detection than AFP and TGF-β1 mRNA. However, these results need further validation studies.