Wang Huimin, Yang Xiaoang, Sun Guiying, Yang Qian, Cui Chi, Wang Xiao, Ye Hua, Dai Liping, Shi Jianxiang, Zhang Jianying, Wang Peng
Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Front Oncol. 2021 Sep 10;11:661043. doi: 10.3389/fonc.2021.661043. eCollection 2021.
The study aims to explore the diagnostic value of anti-GNA11 autoantibody in esophageal squamous cell carcinoma (ESCC) from multiple levels. Autoantibody against GNA11 with the highest diagnostic performance was screened out from the customized protein microarray. A total of 486 subjects including ESCC patients and matched normal controls were recruited in the verification and validation phases by using enzyme-linked immunosorbent assay (ELISA). Western blotting analysis was used to verify the ELISA results. Immunohistochemistry (IHC) was used to evaluate GNA11 expression in ESCC tissues and para-tumor tissues. In addition, a bioinformatics approach was adopted to investigate the mRNA expression of GNA11 in ESCC. Results indicated that the level of anti-GNA11 autoantibody in ESCC patients was significantly higher than that in the normal controls, and it can be used to distinguish ESCC patients from normal individuals in clinical subgroups ( < 0.05), as revealed by both ELISA and Western blotting. The receiver operating characteristic (ROC) curve analysis showed that anti-GNA11 autoantibody could distinguish ESCC patients from normal controls with an area under the ROC curve (AUC) of 0.653, sensitivity of 10.96%, and specificity of 98.63% in the verification cohort and with an AUC of 0.751, sensitivity of 38.24%, and specificity of 88.82% in the validation cohort. IHC manifested that the expression of GNA11 can differentiate ESCC tissues with para-tumor tissues ( < 0.05), but it cannot be used to differentiate different pathological grades and clinical stages ( > 0.05). The mRNA expression of GNA11 in ESCC patients and normal controls was different with a bioinformatics mining with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data in Gene Expression Profiling Interactive Analysis (GEPIA). In summary, anti-GNA11 autoantibody has the potential to be a new serological marker in the diagnosis of ESCC.
本研究旨在从多个层面探索抗GNA11自身抗体在食管鳞状细胞癌（ESCC）中的诊断价值。从定制的蛋白质微阵列中筛选出诊断性能最高的抗GNA11自身抗体。在验证和确认阶段，通过酶联免疫吸附测定（ELISA）招募了包括ESCC患者和匹配的正常对照在内的486名受试者。采用蛋白质印迹分析来验证ELISA结果。免疫组织化学（IHC）用于评估ESCC组织和癌旁组织中GNA11的表达。此外，采用生物信息学方法研究ESCC中GNA11的mRNA表达。结果表明，ESCC患者中抗GNA11自身抗体水平显著高于正常对照，ELISA和蛋白质印迹均显示，在临床亚组中它可用于区分ESCC患者与正常个体（<0.05）。受试者工作特征（ROC）曲线分析表明，在验证队列中，抗GNA11自身抗体可区分ESCC患者与正常对照，ROC曲线下面积（AUC）为0.653，敏感性为10.96%，特异性为98.63%；在确认队列中，AUC为0.751，敏感性为38.24%，特异性为88.82%。免疫组织化学显示，GNA11的表达可区分ESCC组织与癌旁组织（<0.05），但不能用于区分不同的病理分级和临床分期（>0.05）。通过在基因表达谱交互式分析（GEPIA）中利用癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据进行生物信息学挖掘，发现ESCC患者和正常对照中GNA11的mRNA表达存在差异。总之，抗GNA11自身抗体有潜力成为ESCC诊断中的一种新的血清学标志物。
