Immunodiagnostic Value of Combined Detection of Autoantibodies to Tumor‐associated Antigens as Biomarkers in Pancreatic Cancer

Abstract

Previous studies demonstrated that cancer sera contain antibodies, which react with a unique group of autologous cellular antigens called tumour‐associated antigens (TAAs). This study determines whether a panel of TAAs would enhance antibody detection and be a useful approach in pancreatic cancer (PC) detection and diagnosis. The panel of TAAs was composed of six TAAs including p53, p16, p62, survivin, Koc and IMP1 full‐length recombinant proteins. Enzyme‐linked immunosorbent assay (ELISA) was used to detect antibodies against these six TAAs in 23 sera from patients with PC and also 23 sera from normal individuals. Antibody frequency to any individual TAA in PC was variable and ranged from 14.7% to 30.4%. With the successive addition of TAAs to a final total of six antigens, there was a stepwise increase in positive antibody reactions reaching a sensitivity of 60.9% and a specificity of 87.0% in PC. Positive and negative likelihood ratio were 4.685 and 0.449, respectively. Positive and negative predictive values were, respectively, 82.4% and 69.0%. Agreement rate and Kappa value were 73.9% and 0.478, respectively. The data from this study support our previous hypothesis that using a panel of appropriately selected TAAs can enhance autoantibody detection in immunodiagnosis of PC. In 15 PC sera with carbohydrate antigen 19‐9 (CA19‐9) negative, 6 (40%) were found to have anti‐TAA (anti‐tumour associated antigens) antibodies. When CA19‐9 and anti‐TAAs were used together as markers in PC detection, the diagnostic sensitivity could be raised from 60.9% to 69.6%. Anti‐TAA and CA19‐9 were independent markers, and the simultaneous use of these two markers could raise the sensitivity of PC detection.

Anti-heat shock protein autoantibody profiling in breast cancer using customized protein microarray

“…Furthermore, due to the heterogeneity of tumor and individual immune response, detection of one single autoantibody cannot provide efficient analysis for cancer diagnosis, while combining a panel of autoantibodies can greatly increase diagnosis sensitivity. Our results showed that the combination of 7 autoantibodies achieved good sensitivity as well as reasonable high specificity, which is comparable with other studies obtained through ELISA [41][42][43][44]. Moreover, compared to ELISA, our customized antigen microarray is capable of providing high throughput data by consuming smaller sample amounts.…”

Autoimmune response to PARP and BRCA1/BRCA2 in cancer

“…So we have assumed that the drawback can be overcome by using a panel of carefully selected TAAs and that different types of cancer may require different panels of TAAs to achieve the sensitivity and specificity required to make immunodiagnosis a feasible adjunct to tumor diagnosis. Our previous publication [ 12 , 31 ] also indicated that TAAs mini-array seems to be supplementary serological markers for the diagnosis of cancer. Many of these antigen-antibody systems are not found to be useful in differentiating cancer and normal control.…”

Serum Anti-CCNY Autoantibody Is an Independent Prognosis Indicator for Postoperative Patients with Early-Stage Nonsmall-Cell Lung Carcinoma

“…It is reported to be a useful approach for cancer detection and diagnosis by detecting autoantibody using recombinant protein [18, 23, 24]. Therefore, we cloned and expressed a CCNY fusion protein in E. coli BL21 (DE3), established an indirect ELISA method, and analyzed the levels of anti-CCNY autoantibodies in the sera of 264 patients with NSCLC who had not yet undergone treatment, 103 patients with tuberculosis, and 89 healthy controls.…”