Screening of autoantibodies as biomarkers in the serum of renal cancer patients based on human proteome microarray

基于人类蛋白质组微阵列筛选肾癌患者血清中自身抗体作为生物标志物

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作者:Yangyang Sun, Chengxi Liu, Huidong Zhong, Chenguang Wang, Haibo Xu, Wei Chen

Abstract

The autoantibody in patients' serum can act as a biomarker for diagnosing cancer, and the differences in autoantibodies are significantly correlated with the changes in their target proteins. In this study, 16 renal cancer (RC) patients were assigned to the disease group, and 16 healthy people were assigned to the healthy control (HC) group. The human proteome microarray consisting of>19,500 proteins was used to examine the differences in IgG and IgM autoantibodies in sera between RC and HC. The comparative analysis of the microarray results shows that 101 types of IgG and 25 types of IgM autoantibodies are significantly higher in RC than in HC. Highly responsive autoantibodies can be candidate biomarkers (e.g., anti-KCNAB2 IgG and anti-RCN1 IgM). Extensive enzyme-linked immunosorbent assay (ELISA) was performed to screen sera in 72 RC patients and 66 healthy volunteers to verify the effectiveness of the new autoantibodies. The AUCs of anti-KCNAB2 IgG and anti-GAPDH IgG were 0.833 and 0.753, respectively. KCNAB2 achieves high protein expression, and its high mRNA level is confirmed to be an unfavorable prognostic marker in clear cell renal cell carcinoma (ccRCC) tissues. This study suggests that the high-throughput human proteome microarray can effectively screen autoantibodies in serum as candidate biomarkers, and their corresponding target proteins can lay a basis for the in-depth investigation into renal cancer.

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