Department of Epidemiology and Health Statistics & Henan Key Laboratory for Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.
Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Cancer Sci. 2019 Jun;110(6):1829-1841. doi: 10.1111/cas.14013. Epub 2019 May 7.
The present study aimed to select anti-tumor-associated antigen (TAA) autoantibodies as biomarkers in the immunodiagnosis of gastric adenocarcinoma (GAC) by the recursive partitioning approach (RPA) and further construct and evaluate a predictive model. A case-control study was designed including 407 GAC patients as the case group and 407 normal controls. In addition, 67 serial serum samples from 25 GAC patients were collected at different time points before and after gastrectomy treatment. Autoantibodies against 14 TAA were measured in sera from all subjects by enzyme immunoassay. Finally, RPA resulted in the selection of nine-panel TAA (c-Myc, p16, HSPD1, PTEN, p53, NPM1, ENO1, p62, HCC1.4) from all detected TAA in the case-control study; the classification tree based on this nine-TAA panel had area under curve (AUC) of 0.857, sensitivity of 71.5% and specificity of 71.3%; The optimal panel also can identify GAC patients at an early stage from normal individuals, with AUC of 0.737, sensitivity of 64.9% and specificity of 70.5%. However, frequencies of the nine autoantibodies showed no correlation with GAC stage, tumor size, lymphatic metastasis or differentiation. GAC patients positive for more than two autoantibodies in the nine-TAA panel had a worse prognosis than that of the GAC patients positive for no or one antibody. Titers of 10 autoantibodies in serial serum samples were significantly higher in GAC patients after surgical resection than before. In conclusion, this study showed that the panel of nine multiple TAAs could enhance the detection of anti-TAA antibodies in GAC, and may be potential prognostic biomarkers in GAC.
本研究旨在通过递归分区方法(RPA)选择抗肿瘤相关抗原(TAA)自身抗体作为胃腺癌(GAC)免疫诊断的生物标志物,并进一步构建和评估预测模型。设计了一项病例对照研究,纳入 407 例 GAC 患者作为病例组,407 例正常对照。此外,从 25 例 GAC 患者中收集了 67 份不同时间点(手术前后)的系列血清样本。采用酶联免疫吸附试验检测所有受试者血清中针对 14 种 TAA 的自身抗体。最终,RPA 从病例对照研究中所有检测到的 TAA 中选择了九个 TAA 面板(c-Myc、p16、HSPD1、PTEN、p53、NPM1、ENO1、p62、HCC1.4);基于该九个 TAA 面板的分类树具有 0.857 的曲线下面积(AUC),敏感性为 71.5%,特异性为 71.3%;该最佳面板还可以从正常个体中识别出早期 GAC 患者,AUC 为 0.737,敏感性为 64.9%,特异性为 70.5%。然而,九个自身抗体的频率与 GAC 分期、肿瘤大小、淋巴转移或分化无关。在九个 TAA 面板中检测到两个以上自身抗体阳性的 GAC 患者预后比检测到一个或没有自身抗体阳性的 GAC 患者差。手术后 GAC 患者的 10 种自身抗体滴度明显高于手术前。总之,本研究表明,该多 TAA 面板可以提高 GAC 中抗 TAA 抗体的检测,可能是 GAC 的潜在预后生物标志物。