亲环蛋白A 在肝细胞癌中的表达及临床意义

Expression and clinical significance of cyclophilin in hepatocellular carcinoma

摘要:

目的 探讨亲环蛋白A（CyPA）在肝细胞癌（HCC）及血清中的表达及临床意义。方法 收集80 例术后经病理证实为HCC 的肝癌组织、对应癌旁组织及血清标本，另选取同期健康体检者血清标本80 例做 为对照。采用实时荧光定量PCR（qRT-PCR）、Western blot 和免疫组织化学法检测肝癌组织及癌旁组织中 CyPA 的表达水平；ELISA 检测HCC 和健康对照者血清中CyPA 的含量；分析肝癌组织和患者血清中CyPA 含 量与临床病理特征的关系；受试者工作曲线（ROC）分析比较血清AFP 和CyPA 单独或联合对肝癌的诊断价 值。结果 肝癌组织中CyPA mRNA 和蛋白的相对表达水平为（5.66±1.77）和（3.20±1.08），高于癌旁组织的 （1.13±0.27）和（0.74±0.22）（P <0.05）；肝癌组织CyPA 阳性率为77.5%（60/80），高于癌旁组织CyPA 阳性率 28.75%（23/80）（P <0.05）；HCC 患者血清中CyPA 含量为（79.75±17.09）ng/ml，高于健康对照（16.0±63.46） ng/ml（P <0.05）。相关性分析结果显示，不同年龄、性别、肿瘤大小和AFP 含量的患者的CyPA 阳性率，差异 无统计学意义（P >0.05），不同血管浸润、肿瘤包膜是否完整、不同TNM 分期及不同Edmondson 分级的CyPA 阳性率，差异有统计学意义（P <0.05）；不同年龄、性别、肿瘤大小的患者的血清中CyPA 含量，差异无统计学 意义（P >0.05）；不同血管浸润、肿瘤包膜是否完整、不同TNM 分期、不同AFP 含量及不同Edmondson 分级 的患者的血清中CyPA 含量，差异有统计学意义（P <0.05）；ROC 曲线显示AFP 单独诊断的敏感性为82.1%， 特异性为79.3%，曲线下面积为0.813（95%CI ：0.695，0.931）；CyPA 单独诊断的敏感性为92.6%，特异性为 70.3%，曲线下面积为0.798（95%CI ：0.654，0.943）；而AFP 和CyPA 两者联合诊断的敏感性为80.9%，特异性 为90.7%，曲线下面积为0.909（95%CI ：0.833，0.984）。结论 CyPA 在HCC 组织和血清中高表达，且与临床病 理特征相关，可能作为HCC 诊断潜在的肿瘤标志物。

Abstract:

Objective To investigate the expression and clinical significance of cyclophilin A (CyPA) in hepatocellular carcinoma (HCC) patients. Methods Totally 80 cases of hepatocellular carcinoma, who were confirmed by postoperative histology, were involved in this study. Tumor tissue, corresponding para-cancerous tissues and serum specimens were collected for further analysis. Totally 80 healthy individuals were selected as control group. RT-qPCR, Western blotting and immunohistochemistry (IHC) were performed to measure expression of CyPA in HCC tissues and para-cancerous tissues. Serum levels of CyPA were determined with ELISA. Relationship between CyPA and clinical characteristics was identified by statistical analysis. Receiver operating characteristics (ROC) analysis compaled the diagnostic value of serum AFP and CyPA. Results Expression levels of CyPA on mRNA and protein levels in HCC patients were increased significantly compared with those in para-cancerous tissue [(5.66 ± 1.77) vs (1.13 ± 0.27), P < 0.05; (3.20 ± 1.08) vs (0.74 ± 0.22), P < 0.05, respectively]. The positive rate of CyPA in cancer tissue increased greatly when compared with para-cancerous tissue [77.5% (60/80) vs (28.75%, 23/80), P < 0.05]. Serum level of CyPA in HCC patients was elevated significantly compared with that in healthy control group [(79.75 ± 17.09) ng/ml vs (16.06 ± 3.46) ng/ml (P < 0.05)]. Correlation analysis showed that age, gender, tumor size or AFP concentration was not associated with positive rate of CyPA in tumor tissue or serum concentration of CyPA (P > 0.05). Vascular invasion, tumor capsule integrity, AFP concentration and different TNM staging was closely associated with positive rate of CyPA in tumor tissue and serum concentration of CyPA (P < 0.05). ROC curve indicated that the sensitivity and specificity of AFP was 82.1% and 79.3%, respectively; area under the curve was 0.813 (95% CI: 0.695, 0.931). Sensitivity and specificity of CyPA was 92.6% and 70.3%, respectively; area under the curve was 0.798 (95% CI: 0.654, 0.943). The sensitivity of combination of AFP and CyPA was 80.9% and 90.7%, and the area under the curve was 0.909 (95% CI: 0.833, 0.984). Conclusions CyPA is highly expressed in HCC tissues and serum, and is closely related to clinical characteristics. It may serve as a diagnostic biomarker of HCC .