Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Department of Urology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen 518039, China.
Acta Biochim Biophys Sin (Shanghai). 2022 Dec 25;54(12):1909-1916. doi: 10.3724/abbs.2022189.
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.
患者血清中的自身抗体可以作为诊断癌症的生物标志物,自身抗体的差异与靶蛋白的变化显著相关。在这项研究中,将 16 名肾癌(RC)患者分配到疾病组,将 16 名健康人分配到健康对照组(HC)。使用包含>19500 种蛋白质的人类蛋白质组微阵列检测 RC 和 HC 血清中 IgG 和 IgM 自身抗体的差异。微阵列结果的比较分析表明,RC 中 101 种 IgG 和 25 种 IgM 自身抗体明显高于 HC。高反应性自身抗体可以作为候选生物标志物(例如,抗-KCNAB2 IgG 和抗-RCN1 IgM)。进行了广泛的酶联免疫吸附试验(ELISA)以筛选 72 名 RC 患者和 66 名健康志愿者的血清,以验证新自身抗体的有效性。抗-KCNAB2 IgG 和抗-GAPDH IgG 的 AUC 分别为 0.833 和 0.753。KCNAB2 实现了高蛋白质表达,其高 mRNA 水平被证实是透明细胞肾细胞癌(ccRCC)组织中不利的预后标志物。本研究表明,高通量人类蛋白质组微阵列可有效筛选血清中的自身抗体作为候选生物标志物,其相应的靶蛋白可为深入研究肾癌奠定基础。