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血清抗骨桥蛋白自身抗体作为肝细胞癌患者一种新型的诊断和预后生物标志物。

Serum anti-osteopontin autoantibody as a novel diagnostic and prognostic biomarker in patients with hepatocellular carcinoma.

作者信息

Ying Xia, Zhao Yue, Wang Jun-Lan, Zhou Xia, Zhao Jing, He Chen-Chen, Guo Xi-Jing, Jin Gui-Hua, Wang Li-Juan, Zhu Qing, Han Su-Xia

机构信息

Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, P.R. China.

Department of Oncology Radiotherapy, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.

出版信息

Oncol Rep. 2014 Oct;32(4):1550-6. doi: 10.3892/or.2014.3367. Epub 2014 Jul 30.

DOI:10.3892/or.2014.3367
PMID:25109745
Abstract

Osteopontin (OPN) is a secreted phosphorylated and glycosylated protein, which plays an important role in carcinogenesis and metastasis. In hepatocellular carcinoma (HCC), OPN is being investigated either as a therapeutic target gene or as a biomarker for diagnosis. Yet, the role of the anti-OPN autoantibody in HCC remains unclear. In the present study, the level of serum anti-OPN autoantibody in HCC was analyzed by enzyme-linked immunosorbent assay. Immunohistochemistry (IHC) was also performed to analyze protein expression profiles and the prognostic significance of OPN in HCC. In this study, the prevalence and titer of anti-OPN autoantibodies in HCC were significantly higher than these values in normal human serum (NHS) (P=0.001, P=0.000, respectively). When both α-fetoprotein and the autoantibody against OPN were used simultaneously as diagnostic biomarkers, the sensitivity was up to 65%. In IHC, 59 of the 83 (65.6%) HCC specimens expressed OPN with cytoplasmic positive staining. The overall survival (OS) of HCC patients with OPN-positive tumors was 28.81 months compared to 39.37 months for HCC patients with OPN-negative tumors (P<0.01). Furthermore, multivariate analysis showed that OPN overexpression was the strongest independent adverse prognostic factor for OS (P=0.02). Taken together, our data indicate that the anti-OPN autoantibody may be a supplementary serological biomarker for HCC, and is correlated with poor prognosis in HCC patients.

摘要

骨桥蛋白(OPN)是一种分泌型磷酸化糖蛋白,在肿瘤发生和转移中起重要作用。在肝细胞癌(HCC)中,OPN正作为治疗靶点基因或诊断生物标志物进行研究。然而,抗OPN自身抗体在HCC中的作用仍不清楚。在本研究中,采用酶联免疫吸附测定法分析了HCC患者血清抗OPN自身抗体水平。还进行了免疫组织化学(IHC)分析HCC中OPN的蛋白表达谱及其预后意义。在本研究中,HCC患者抗OPN自身抗体的患病率和滴度显著高于正常人血清(NHS)中的这些值(分别为P = 0.001,P = 0.000)。当甲胎蛋白和抗OPN自身抗体同时用作诊断生物标志物时,敏感性高达65%。在免疫组织化学中,83例HCC标本中有59例(65.6%)OPN表达呈细胞质阳性染色。OPN阳性肿瘤的HCC患者总生存期(OS)为28.81个月,而OPN阴性肿瘤的HCC患者为39.37个月(P<0.01)。此外,多变量分析表明OPN过表达是OS最强的独立不良预后因素(P = 0.02)。综上所述,我们的数据表明抗OPN自身抗体可能是HCC的一种补充血清学生物标志物,并且与HCC患者的不良预后相关。

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