肝细胞癌（HCC）是一种在世界范围内发病率很高的癌症，因此HCC的早期诊断对于HCC治疗以及获得最佳预后效果具有重要意义。

　　在来自中国科学家的一项最新研究中，研究人员利用志愿者血清对HCC肿瘤相关抗原（TAA）进行了免疫蛋白组学的分析筛选。通过对914名血清中可检测到α甲胎蛋白的志愿者进行蛋白质芯片分析，他们利用自身抗体检测的方法发现22个候选肿瘤相关抗原。

　　研究人员通过回顾临床资料对这些抗原在HCC，慢性间质性肝炎，慢性肝炎疾病和健康人对照中的表达情况进行了评估，结果证明有12个候选TAA在HCC病人和对照组之间存在统计学差异，其中，CENPF,HSP60和IMP-2在早期HCC发展中具有比较明显的差异性表达。并且在α甲胎蛋白阴性的早期HCC病人中，分别有73.6%和79.3%的病人存在CENPF和HSP60自身抗体阳性。

　　早期阶段的HCC可能会触发身体内肿瘤相关的自身免疫反应。因此，检测血清中针对TAA的自身抗体可以作为α甲胎蛋白检测的辅助手段，对于提高早期HCC诊断率具有重要意义。

　　DOI: http://dx.doi.org/10.1016/j.ebiom.2015.03.010

　　An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

　　Yu Hong1, Jiang Long1, Hai Li1, Shuhong Chen, Qiqi Liu, Bei Zhang, Xiaomin He, Yan Wang, Hongyi Li, Yimei Li, Tao Zhang, Chenzhen Lu, Hao Yan, Minli Zhang, Qing Li, Bangwei Cao, Zhigang Bai, Jin Wang, Zhongtao Zhang, Shengtao Zhu, Jiasheng Zheng, Xiaojuan Ou, Hong Ma, Jidong Jia, Hong Youcorrespondenceemail, Shengqi Wangcorrespondenceemail, Jian Huang

　　Abstract

　　Background

　　Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis.

　　Methods

　　Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing protein antigens of the candidate TAAs. Analyses were done by using receiver operating characteristics (ROC) to calculate diagnostic accuracy.

　　Findings

　　Twenty-two candidate TAAs were assessed by protein microarray analysis in 914 participants with serum α-fetoprotein (AFP) available. Twelve candidate TAAs were statistically different in signal intensity between HCC and controls. Among them, CENPF, HSP60 and IMP-2 showed AUC (area under the curve) values of 0.826, 0.764 and 0.796 respectively for early HCC. The highest prevalence of autoantibody positivity was observed in HCC cases with BCLC tumor stage A, well-differentiated histology and Child-Pugh grade C. Specifically, 73.6% or 79.3% cases of early HCC with negative AFP were positive for autoantibody to CENPF or HSP60.

　　Interpretation

　　Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC.