Ying Xia, Han Su-Xia, He Chen-Chen, Zhou Cong-Ya, Dong Yi-Ping, Cai Meng-Jiao, Sui Xin, Ma Cheng-Xian, Sun Xiao, Zhang Yuan-Yuan, Gou Wen-Li, Mason Clifford, Zhu Qing
Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
Department of Gynecological Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Oncotarget. 2017 Apr 11;8(15):24828-24839. doi: 10.18632/oncotarget.15192.
To identify Heptocellular carcinoma (HCC) associated antigens by proteomics, and validate whether autoantibodies against tumor-associated antigens (TAAs) could be used for diagnosis and conditional monitoring.
The 78 kDa glucose regulated protein (GRP78) was selected as a candidate TAA. The titers of autoantibodies against 78 kDa glucose regulated protein (GRP78) from patients with HCC, liver cirrhosis (LC), and chronic hepatitis (CH) were significantly higher than that from normal controls (P<0.05, P<0.001, and P<0.01, respectively). The expression of autoantibodies against GRP78 was associated with clinical stage (P<0.01), portal vein invasion (P<0.05), and metastasis (P<0.05). The expression of anti-GRP78 antibodies was significantly higher 1 month after surgery in recurrent patients who had accepted hepatic resection 1 month after surgery compared to patients who had surgery before surgery or within 1 week after surgery (P<0.01 and P<0.001). Immunohistochemistry (IHC) showed higher expression of GRP78 in HCC compared to the non-HCC liver tissues (P <0.05).
HCC serum with high titer of autoantibodies against TAAs were screened and used for a proteome-based approach to identify HCC associated antigens. Indirect enzyme-linked immunoassay (ELISA) was used to detect the corresponding autoantibodies against TAAs.
GRP78 is an autoantigen that could stimulate autoimmune responses and serve as a potential marker for recurrent and metastatic progression in HCC.
通过蛋白质组学鉴定肝细胞癌（HCC）相关抗原，并验证针对肿瘤相关抗原（TAA）的自身抗体是否可用于诊断和病情监测。
选择78 kDa葡萄糖调节蛋白（GRP78）作为候选TAA。肝癌（HCC）、肝硬化（LC）和慢性肝炎（CH）患者中针对78 kDa葡萄糖调节蛋白（GRP78）的自身抗体滴度显著高于正常对照组（分别为P<0.05、P<0.001和P<0.01）。针对GRP78的自身抗体表达与临床分期（P<0.01）、门静脉侵犯（P<0.05）和转移（P<0.05）相关。与术前或术后1周内接受肝切除的患者相比，术后1个月复发且接受肝切除的患者术后1个月抗GRP78抗体的表达显著更高（P<0.01和P<0.001）。免疫组织化学（IHC）显示，与非HCC肝组织相比，HCC中GRP78的表达更高（P<0.05）。
筛选出针对TAA具有高滴度自身抗体的HCC血清，并用于基于蛋白质组学的方法来鉴定HCC相关抗原。采用间接酶联免疫吸附测定（ELISA）检测针对TAA的相应自身抗体。
GRP78是一种可刺激自身免疫反应的自身抗原，可作为HCC复发和转移进展的潜在标志物。
