血清颗粒蛋白前体作为潜在肝癌诊断标志物的临床价值研究

Clinical value of serum progranulin as a potential marker for the detection of hepatocellular carcinoma

目的探讨血清颗粒蛋白前体(progranulin,PGRN)在原发性肝细胞癌(hepatocellular carcinoma,HCC)诊断中的潜在应用价值。方法首先从基因表达综合数据库(gene expression omnibus,GEO)下载肝癌表达谱数据集(GSE55092和GSE121248),分析PGRN在HCC组织和癌旁组织中的表达水平。此外,本研究招募50例HCC患者(HCC组)、20例慢性乙型肝炎(chronic hepatitis B,CHB)患者(CHB组)、20例肝硬化(liver cirrhosis,LC)患者(LC组)和30例正常对照者(NC组)。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清中PGRN和甲胎蛋白(alpha-fetoprotein,AFP)的含量。采用受试者工作特征曲线(receiver operating characteristic curve,ROC)计算早期诊断HCC的曲线下面积(area under the curve,AUC),分析血清PGRN和AFP对诊断HCC的潜在临床应用价值。结果在GEO数据集GSE55092和GSE121248中,HCC组织的PGRN表达水平均显著高于癌旁组织(P<0.05)。在血清样本中,HCC组血清AFP和PGRN蛋白水平显著高于NC组、CHB组和LC组(P<0.05)。ROC曲线显示,PGRN具有鉴别诊断HCC的潜在临床应用价值(P<0.05),HCC患者血清PGRN与AFP联合检测诊断HCC的AUC为0.97(0.93~0.98)、灵敏度为92.0%、特异度为96.9%,均高于血清PGRN、AFP单独检测HCC时的AUC、灵敏度和特异度值。结论PGRN有作为HCC早期诊断血清标志物的潜力,AFP和PGRN联合检测对HCC具有更高的诊断潜能,有望用于临床筛查早期HCC。

Objective To evaluate the potential clinical value of progranulin(PGRN)in the diagnosis of primary hepatocellular carcinoma(HCC).Methods We downloaded HCC gene expression profiles from Gene Expression Omnibus(GEO)datasets(GSE55092,GSE121248)and compared PGRN expressions in the HCC tissues with that in the non-tumor liver tissues.In addition,we recruited 50 patients with HCC and designated them as the HCC group,20 patients with chronic hepatitis B(the CHB group)and another 20 patients with liver cirrhosis(the LC group)and 30 normal control subjects(the NC group).The PGRN and alpha-fetoprotein(AFP)expressions in serum were detected by enzyme-linked immunosorbent assay(ELISAs).The receiver operating characteristic curve(ROC)was used to calculate the area under the curve(AUC)and analyze the potential clinical value of serum PGRN and AFP in the diagnosis of HCC.Results In both the 2 GEO datasets(GSE55092,GSE121248),the PGRN expression levels in the HCC tissues were significantly higher than those in the non-tumor liver tissues(P<0.05).The serum AFP and PGRN protein expression levels in the HCC group were significantly higher than those in the NC,CHB and LC groups(all P<0.05).The ROC curve indicated that serum PGRN displayed potential clinical value in the diagnosis of HCC(P<0.05).When combining the serum PGRN with AFP in HCC patients,the AUC was 0.97(0.93-0.98),the sensitivity was 92.0%and the specificity was 96.9%,which were all higher than those of the PGRN or AFP alone.Conclusion PGRN might be a potential serum biomarker for the detection of HCC.The combination of AFP and PGRN has a higher performance for the detection of HCC,and might hold good promise for the detection of HCC clinically.