Oncotarget

Research Papers:

Autoantibodies against glucose-regulated protein 78 as serological biomarkers in metastatic and recurrent hepatocellular carcinoma

Xia Ying _, Su-xia Han, Chen-chen He, Cong-ya Zhou, Yi-ping Dong, Meng-jiao Cai, Xin Sui, Cheng-xian Ma, Xiao Sun, Yuan-yuan Zhang, Wen-li Gou, Clifford Mason and Qing Zhu

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Oncotarget. 2017; 8:24828-24839. https://doi.org/10.18632/oncotarget.15192

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Abstract

Xia Ying1,2, Su-xia Han3, Chen-chen He3, Cong-ya Zhou1, Yi-ping Dong3, Meng-jiao Cai1, Xin Sui3, Cheng-xian Ma1, Xiao Sun3, Yuan-yuan Zhang1, Wen-li Gou4, Clifford Mason5, Qing Zhu1

1Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi’an, Shannxi, P.R. China

2Department of Gynecological Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China

3Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University Medical College, Xi’an, Shannxi, P.R. China

4Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University Medical College, Xi’an, Shannxi, P.R. China

5Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, Kansas, USA

Correspondence to:

Qing Zhu, email: [email protected]

Keywords: heptocellular carcinoma (HCC), tumor associated antigens (TAA), proteomics, autoantibodies, biomarker

Received: June 03, 2016    Accepted: December 05, 2016    Published: February 08, 2017

ABSTRACT

Purpose: 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.

Results: 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).

Materials and Methods: 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.

Conclusion: GRP78 is an autoantigen that could stimulate autoimmune responses and serve as a potential marker for recurrent and metastatic progression in HCC.


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