分泌型聚集素表达临床病理学特征及对肝细胞性肝癌的诊断和预后价值

Clinicopathologic features of secretory clusterin expression and its diagnostic and prognostic values for hepatocellular carcinoma

目的 :探讨分泌型聚集素(secretory clusterin,s CLU)在肝细胞性肝癌(hepatocellular carcinoma,HCC)组织中的表达特征及其诊断和预后价值。方法:采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测良、恶性肝病患者血清s CLU水平,与甲胎蛋白(α-fetoprotein,AFP)比较以评价对HCC的诊断价值;以组织芯片技术及免疫组织化学法观察HCC及癌旁组织s CLU的表达与胞内分布及对HCC预后的临床价值。结果:HCC患者血s CLU平均水平为120.1μg/m L明显高于肝硬化97.8μg/m L、慢性肝炎106.3μg/m L及正常对照90.0μg/m L(P<0.01);受试者工作曲线(receiver operating curve,ROC)面积s CLU为0.771,AFP为0.750;诊断HCC阳性率s CLU为82.4%,AFP为63.2%,两者联合检测可提高至93.1%。s CLU主要定位于细胞质,癌组织过表达,癌旁组低表达;癌组阳性率为77.3%,明显高于癌旁组的36.1%(P<0.001),与淋巴结转移、TNM分期及患者生存时间密切相关。结论:s CLU过表达与HCC进展密切相关,可作为一个潜在的HCC诊断及预后指标。

Objective： To investiga te the expression characteristics of secretory clusterin （ sCLU ） and its diagnosis and prognostic value for hepatocellular carcinoma （ HCC ） . Methods： Serum sCLU levels were determined by enzyme linked immunosorbent assay（ELISA） in patients with benign or malignant liver disease, and evaluated diagnostic value compared withα-fetoprotein （ AFP ） level . The sCLU expression in HCC or adjacent tissues was observed by tissue microarray combing immunohistochemistry for analyzing intercellular distribution and prognostic value. Results： Circulating sCLU level in HCC patients （120.1μg/mL） was significantly higher than that in any of cirrhosis（97.8μg/mL）, chronic hepatitis（106.3μg/mL）, or normal control（90.0μg/mL）（P〈0.001）. The area of receiver operating curve（ROC） and the sensitivity of diagnostic HCC were 0.771 and 84% in sCLU, while 0.750 and 63.2% in AFP, and combining detection of both rose up to 93.1% for HCC. The major expression of hepatic sCLU was located in cytoplasm, with over-expression in HCC（77.3%） significantly higher than that in their surrounding tissues（36.1%）（ P〈0 . 001 ） and closely related with lymphatic metastasis, TNM staging and survival time of HCC patients. Conclusion： Over-expression of sCLU was associated with the progression of HCC, and should be a potential diagnostic and prognostic biomarker for HCC.