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 mini‐array of multiple TAAs would enhance antibody detection and be a useful approach in colon cancer detection and diagnosis. The mini‐array of multiple TAAs was composed of five TAAs including Imp1, p62, Koc, p53 and c‐myc full‐length recombinant proteins. Enzyme‐linked immunosorbent assay (ELISA) was used to detect antibodies against these five TAAs in 46 sera from patients with colon cancer and also 58 sera from normal individuals. Antibody frequency to any individual TAA in colon cancer was variable and ranged from 15.2% to 23.9%. With the successive addition of TAAs to a final total of five antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 60.9% and a specificity of 89.7% in colon cancer. Positive and negative likelihood ratio was 5.91 and 0.43 respectively, which showed that the clinical diagnostic value of parallel assay of five TAAs was high. Positive and negative predictive values were respectively 82.4% and 74.3% indicating that parallel assay of five TAAs raised the diagnostic precision greatly. Agreement rate and Kappa value were 76.9% and 0.52 respectively, which indicated that the observed value of this assay had middle range coincidence with actual value. The data from this study further support our previous hypothesis that detection of autoantibodies for diagnosis of certain type of cancer can be enhanced by using a mini‐array of several TAAs as target antigens. In 19 colon cancer sera with carcinoembryonic antigen (CEA) negative, 11 (57.9%) were found to have anti‐TAA antibodies. When CEA and anti‐TAAs were used together as markers in colon cancer detection, the diagnostic sensitivity could be raised from 60.9% to 82.6%. A customized antigen mini‐array using a panel of appropriately selected TAAs can enhance autoantibody detection in immunodiagnosis of colon cancer. Anti‐TAA and CEA were independent markers and the simultaneous use of these two markers significantly raised the sensitivity of colon cancer detection.
Aberrant expression of a zinc transporter ZIP4 in pancreatic ductal adenocarcinoma (PDAC) has been shown to contribute to tumor progression and is a potential target for individualized therapy. The overall objective of this study was to determine whether ZIP4 could serve as a novel diagnostic and prognostic marker in human PDAC, and if it can be assessed by minimally invasive sampling using endoscopic ultrasound guided fine needle aspiration (EUS-FNA). Immunohistochemistry was performed to compare ZIP4 expression in the PDAC samples obtained from EUS-FNA and matched surgical tumors (parallel control). Samples were reported by sensitivity, specificity, and predictive values, all with 95% confidence intervals (CI). A total of 23 cases with both FNA and surgical specimens were evaluated. We found that ZIP4 was significantly overexpressed in tumor cells from both sets of samples. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ZIP4 for the diagnosis of PDAC were 72.9%, 72.5%, 76.1%, and 69.0% in EUS-FNA samples, and were 97.9%, 65.4%, 83.9%, and 94.4% in surgical specimens, respectively. The association between the positive rate of ZIP4 expression in FNA and surgical samples is statistically significant (P=0.0216). Both the intensity and percentage of ZIP4 positive cells from the surgical samples correlated significantly with tumor stage (P=0.0025 and P=0.0002). ZIP4 intensity level in FNA samples was significantly associated with tumor differentiation and patient survival. These results indicate that EUS-FNA is capable of non-operative detection of ZIP4, thus offering the potential to direct pre-operative detection and targeted therapy of PDAC.
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