[The clinical value of serum GPC3 level in predicting recurrence of patients with primary hepatocellular carcinoma].

Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ2=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ2=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ2=4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ2=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.目的： 探讨血清磷脂酰肌醇蛋白聚糖3（glypican-3，GPC3）检测在原发性肝细胞肝癌（hepatocellular carcinoma，HCC）复发预测中的临床应用价值。 方法： 采用单/多因素logistic回归方程，选择2019年3月至2021年1月在复旦大学附属肿瘤医院病理诊断为HCC的患者113例作为实验组，预后共纳入随访时间超过6个月的64例HCC患者；简单随机抽样法入组同期体检中心健康者20名、良性肝病者20例作为对照组（n=40）；血清GPC3采用酶联免疫吸附试验（ELISA）法检测，甲胎蛋白（AFP）采用电化学发光法检测，测定值用［M（Q1，Q3）］表示；探索影响HCC复发的影响因素，利用logistic回归分析GPC3联合其他HCC复发的影响因素在HCC复发判断的准确性。 结果： 本研究中GPC3诊断HCC的灵敏度为61.95%（70/113），AFP为52.21%（59/113），同时，GPC3特异度可达87.50%（35/40），AFP为90.00%（36/40）；进展期、肿瘤最大直径≥3 cm、有脉管癌栓、有门静脉癌栓的HCC患者血清GPC3浓度分别显著高于早期、肿瘤最大直径<3 cm、无脉管癌栓、无门静脉癌栓的HCC患者（Z=2.677、2.848、2.995、2.252，P<0.05），而不同年龄、有无腹水、有无腹膜转移、有无肝硬化、有无肝内转移HCC患者间血清GPC3浓度比较差异均无统计学意义（Z=-1.535、1.011、0.963、0.394、1.510，P>0.05）；单因素分析表明复发组与未复发组年龄、肿瘤大小、有无脉管癌栓、有无腹水、有无腹膜转移、有无肝硬化及甲胎蛋白水平间比较差异均无统计学意义（χ2=2.012、0.119、2.363、1.041、0.318、0.360，Z=0.748，P>0.05）；复发组进展期、有门静脉癌栓者、有肝内转移者比值及GPC3水平均高于未复发组，且差异均有统计学意义（χ2=4.338、11.90、4.338，Z=2.805，P<0.05）；将上述有统计学差异的因素纳入logistic回归模型中，logistic回归分析表明分期、有门静脉癌栓、有肝内转移及GPC3水平与HCC患者复发相关（Wald χ2=4.421、5.681、4.995、4.319，P<0.05），并经拟合回归方程后计算HCC-GPC3预后相关模型Score值，得到回归方程为：OcScore=-2.858+1.563×［分期］+1.664×［肝内转移］+2.942×［门静脉癌栓］+0.776×［GPC3］；绘制HCC-GPC3预后模型的ROC曲线，曲线下面积为0.862，优于单GPC3的0.704，得出模型SCORE的cut-off值为0.700（GPC3 的cut-off值为0.257 mg/L），对HCC预后复发与否的总灵敏度为83.3%，总特异度为82.4%，分别优于GPC3的60.0%与79.4%；本研究发现GPC3高浓度（≥0.257 mg/L）、复发预测模型SCORE高值（≥0.700）的HCC患者中位PFS显著缩短（χ2=12.73、28.16，P<0.05）。 结论： GPC3可能不仅具有HCC鉴别诊断价值，还能作为HCC复发的独立危险指标，结合分期、有无肝内转移、有无门静脉癌栓能更好地预测HCC患者是否复发。.