Zinc-α-2-Glycoprotein: A Candidate Biomarker for Colon Cancer Diagnosis in Chinese Population

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.

Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients

“…Indeed, ZAG concentration has been reported to be increased in colon cancer and permitted a more accurate diagnostic of cancer in combination with traditional markers, such as carcinoembryonic antigen or carbohydrate antigen 19.9. 57 Similar results were found for prostate cancer: serum ZAG concentration was higher in men with prostate cancer than in those with nonmalignant prostate disease or healthy men. 58,59 Herein, we did not find any association between ZAG concentration and cancer-related mortality.…”

Cell Line Secretome and Tumor Tissue Proteome Markers for Early Detection of Colorectal Cancer: A Systematic Review

“…Table 1 and Table 2 present an overview on the characteristics of the participants for the cell line secretome and tumor tissue proteome marker studies, respectively. Twenty-nine studies were conducted in Asia; fourteen in China [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], five each in Taiwan [ 35 , 36 , 37 , 38 , 39 ] and Japan [ 40 , 41 , 42 , 43 , 44 ], four in Korea [ 45 , 46 , 47 , 48 ] and one in Singapore [ 49 ]. Out of 15 studies that were carried out in Europe, six studies were performed in Spain [ 50 , 51 , 52 , 53 , 54 , 55 ], four in Germany [ 56 , 57 , 58 , 59 ] out of which one multicenter study was also carried out in the Czech Republic [ 58 ], and one each in Denmark [ 60 ], France [ 61 ], Ireland [ 62 ], The Netherlands [ 63 ] and Poland [ 64 ].…”

“…Overall, 38 different proteins were included in some of the combinations, with CEA included in eight out of 14 combinations, again being the most commonly reported. From six studies that performed some form of correction for overoptimism [ 25 , 29 , 42 , 58 , 61 , 62 ], Kijanka et al [ 62 ] reported best diagnostic performance (84% sensitivity at 80% specificity) with a 12 protein marker combination using tissue from 43 CRC patients and 19 controls with no neoplasm of colon.…”

Effect of purified fractions from cell culture supernate of high‐density pre‐B acute lymphoblastic leukemia cells (ALL3) on the growth of ALL3 cells at low density

“…It is associated with the cachexia related to cancer . It is involved in prostate cancer , colon cancer , breast carcinoma, gastric cancer , and hepatocellular carcinoma .…”