Abstract
Zinc-α-2-glycoprotein (AZGP1) is a 41-kDa secreted glycoprotein, which has been detected in several malignancies. The diagnostic value of AZGP1 in serum of prostate and breast cancer patients has been reported. Analyzing “The Cancer Genome Atlas” data, we found that in colon cancer AZGP1 gene expression was upregulated at transcriptional level. We hypothesized that AZGP1 could be used as a diagnostic marker of colon cancer. First, we confirmed AZGP1 expression was higher in a set of 28 tumor tissues than in normal colonic mucosa tissues by real-time quantitative PCR and western blot in a Chinese population. We verified that serum concentration of AZGP1 was higher in 120 colon cancer patients compared with 40 healthy controls by ELISA (p < 0.001). Then receiver-operating characteristic (ROC) curve analysis was used to evaluate the predictive diagnostic value of AZGP1 in serum. The area under the curve (AUC) of AZGP1 was 0.742 (p < 0.001, 95% confidence interval (CI) = 0.656–0.827) in between the AUC of carcinoembryonic antigen (CEA) and the AUC of CA19-9, suggesting that predictive diagnostic value of AZGP1 is between CEA and Carbohydrate 19-9 (CA19-9). The combination of AZGP1 with traditional serum biomarkers, CEA and CA19-9, could result in better diagnostic results. To further validate the diagnostic value of AZGP1, a tissue microarray containing 190 samples of primary colon cancer tissue paired with normal colonic tissue was analysed and the result showed that AZGP1 was significantly upregulated in 68.4% (130 of 190) of the primary cancer lesions. In contrast, there was a weakly positive staining in 29.5% (56 of 190) of the normal colonic tissue samples (p < 0.001). Leave-one-out cross-validation was performed on the serum data, and showed that the diagnostic value of AZGP1 had 63.3% sensitivity and 65.0% specificity. Combination of AZGP1, CEA and CA19-9 had improved diagnosis value accuracy with 74.2% sensitivity and 72.5% specificity. These results suggest that AZGP1 is a useful diagnostic biomarker in tissues and serum from a Chinese population.
Highlights
Colon cancer has one of the highest incidence rates among different types of cancers worldwide and remains the second most common cause of cancer-related death in the United States [1,2]
After analysis of the “The Cancer Genome Atlas” (TCGA) data, we found that in colon cancer
Our data showed that AZGP1 expression was upregulated in colon cancer patients at the transcriptional level in the Chinese population (p = 0.015) (Figure S1)
Summary
Colon cancer has one of the highest incidence rates among different types of cancers worldwide and remains the second most common cause of cancer-related death in the United States [1,2]. A proportion of early stage patients receiving surgical resection still relapse, even with combined treatment of adjuvent chemotherapy [3] Many markers such as adenomatous polyposis coli (APC), DNA mismatch repair genes, vascular endothelial growth factors (VEGFs) and their receptors, and, more recently, microRNAs and colon epithelial stem cell markers, have been systematically analyzed for diagnosis and prognosis of colon cancer [7,8,9,10,11,12]. We detected the difference in serum of cancer patients and normal controls by Enzyme-linked immunosorbent assay (ELISA), and made Receiver operating characteristic (ROC) curves to explore the diagnostic value of AZGP1 either alone or combined with the common clinical biomarkers of CEA and CA19-9. We identified AZGP1 as a potential biomarker for colon cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
