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

Abstract

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, HSPD 1, PTEN , p53, NPM 1, ENO 1, p62, HCC 1.4) 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 .

Unlikely role of glycolytic enzyme ��-enolase in cancer metastasis and its potential as a prognostic biomarker

“…Externalisation of a-enolase by cancer cells exposes it to the immune system as a tumour-associated antigen that has been found to induce autoantibody production in cancer patients, including those with acute and chronic leukaemias, melanoma, and lung, breast, gastric and pancreatic cancers [22,45,[73][74][75][76][77][78][79] . In pancreatic cancer, T cells activated by a-enolase-pulsed dendritic cells lysed pancreatic cancer cells, but not normal human keratinocytes in vitro and inhibited CF-PAC-1 tumour growth in vivo [22] .…”

Six autoantibodies as potential serum biomarkers of hepatocellular carcinoma: A prospective multicenter study

“…However, previous reports were small studies, and the prognostic and diagnostic impact on the patients with HCC has not been well evaluated. The prognostic value of serum autoantibodies, including NY‐ESO‐1, p53 and others in cholangiocarcinoma and gastric cancer, has been investigated, but the results are inconclusive 12‐14 . This prospective multicenter study investigated the diagnostic and prognostic impact of autoantibodies against a panel of TAAs, including Sui1, p62, RalA, p53, NY‐ESO‐1 and c‐myc.…”

Discovery and Validation of Serum Autoantibodies Against Tumor-Associated Antigens as Biomarkers in Gastric Adenocarcinoma Based on the Focused Protein Arrays

“…One hundred fifty-four human recombinant proteins provided by CDI Laboratories (Mayaguez) were used to construct the focused protein arrays (BC-BIO, Foshan, China). Among them, 143 proteins were encoded by 115 cancer driver genes (58 tumor suppressor gene and 57 oncogene) ( 16 ) and 11 proteins encoded by 10 genes which were reported to be potential biomarkers by our previous studies ( 17 , 18 ). The quality control of the focused protein arrays was described in our previous study ( 19 ).…”