Using recursive partitioning approach to select tumor‐associated antigens in immunodiagnosis of gastric adenocarcinoma

• Published in: Cancer science Vol. 110; no. 6; pp. 1829 - 1841
• Main Authors: Qin, Jiejie, Wang, Shuaibing, Shi, Jianxiang, Ma, Yan, Wang, Keyan, Ye, Hua, Zhang, Xiaojun, Wang, Peng, Wang, Xiao, Song, Chunhua, Dai, Liping, Wang, Kaijuan, Jiang, Binghua, Zhang, Jianying
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2019; John Wiley and Sons Inc
• Subjects: Adenocarcinoma; Adenocarcinoma - diagnosis; Adenocarcinoma - immunology; Adult; Aged; Aged, 80 and over; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - blood; Antigens, Neoplasm - immunology; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; autoantibody; biomarker; Biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - immunology; Cancer therapies; Carbohydrates; Case-Control Studies; Enzyme immunoassay; Esophagus; Female; Gastrectomy; gastric adenocarcinoma; Gastric cancer; Humans; Immunodiagnosis; Immunoglobulins; Immunologic Tests - methods; Lymphatic system; Male; Medical prognosis; Metastases; Metastasis; Middle Aged; Mortality; Multivariate Analysis; Original; p53 Protein; Patients; Prediction models; PTEN protein; recursive partitioning approach; ROC Curve; Statistical analysis; Stomach Neoplasms - diagnosis; Stomach Neoplasms - immunology; Studies; Surgery; tumor‐associated antigen; Young Adult; China; recursive partitioning approach; autoantibody; gastric adenocarcinoma; tumor-associated antigen; biomarker
• DOI: 10.1111/cas.14013
• ISSN: 1347-9032; 1349-7006

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. Recursive partitioning approach (RPA) is a powerful method for selecting markers in cancer and a panel selected by RPA showed high diagnostic values for gastric adenocarcinoma. Antibody levels showed no correlation with tumor stage, size, or differentiation. Certain anti‐TAA antibodies increased after gastrectomy in gastric adenocarcinoma sera.