Using Serological Proteome Analysis to Identify and Evaluate Anti-GRP78 Autoantibody as Biomarker in the Detection of Gastric Cancer

利用血清学蛋白质组分析鉴定和评估抗 GRP78 自身抗体作为胃癌检测生物标志物

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作者:Jiejie Qin #, Qian Yang #, Hua Ye #, Keyan Wang, Meng Zhang, Jicun Zhu, Xiao Wang, Liping Dai, Peng Wang, Jianying Zhang

Abstract

The serological biomarkers as noninvasive tests are the most promising way for diagnosing gastric cancer (GC). Serological proteome analysis (SERPA) has been used to identify tumor-associated antigens (TAAs) and the corresponding autoantibodies in many studies. To explore the relationship between gastric cancer development and serum autoantibody anti-GRP78 response found by the method of SERPA with the GC cell line AGS, we included two cohorts (133 GC and 133 normal individuals in test group; 300 GC and 300 normal individuals in validation group) of patients with newly diagnosed GC for verification. All GC and normal controls were matched by age and gender. The autoantibody levels of the sera in two cohorts were measured by immunoassay. Finally, the results showed that 78-kDa glucose-regulated protein (GRP78) was identified in GC by SERPA and the level of anti-GRP78 antibody in GC was higher than that in normal individuals in the two cohorts. Receiver operating characteristic (ROC) curve analysis showed similar diagnostic value of anti-GRP78 antibody in test group (AUC: 0.718) and validation group (AUC: 0.666) to identify GC patients from normal individuals. The AUCs of anti-GRP78 autoantibody in the diagnosis of GC patients with different clinical characteristic ranged from 0.676 to 0.773 in test group and ranged from 0.645 to 0.707 in validation group. In conclusion, autoantibody against GRP78 might be a potential diagnostic biomarker. Further large-scale studies will be needed to validate and improve its performance of the sensitivity, specificity, and AUC value in distinguishing GC from other diseases.

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