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Int. J. Mol. Sci. 2015, 16(1), 691-703; doi:10.3390/ijms16010691

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

1
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200000, China
2
Department of Pathology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200000, China
*
Author to whom correspondence should be addressed.
Academic Editor: Camile S. Farah
Received: 12 November 2014 / Accepted: 17 December 2014 / Published: 30 December 2014
(This article belongs to the Special Issue Emerging Classes of Biomarkers for Molecular Diagnostics)
View Full-Text   |   Download PDF [4042 KB, uploaded 30 December 2014]   |  

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. View Full-Text
Keywords: AZGP1 protein; human; colon cancer; clinical marker; tissue array analysis AZGP1 protein; human; colon cancer; clinical marker; tissue array analysis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Xue, Y.; Yu, F.; Yan, D.; Cui, F.; Tang, H.; Wang, X.; Chen, J.; Lu, H.; Zhao, S.; Peng, Z. Zinc-α-2-Glycoprotein: A Candidate Biomarker for Colon Cancer Diagnosis in Chinese Population. Int. J. Mol. Sci. 2015, 16, 691-703.

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