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Zinc-α-2-glycoprotein: a candidate biomarker for colon cancer diagnosis in Chinese population.

Xue Y, Yu F, Yan D, Cui F, Tang H, Wang X, Chen J, Lu H, Zhao S, Peng Z - Int J Mol Sci (2014)

Bottom Line: Zinc-α-2-glycoprotein (AZGP1) is a 41-kDa secreted glycoprotein, which has been detected in several malignancies.In contrast, there was a weakly positive staining in 29.5% (56 of 190) of the normal colonic tissue samples (p < 0.001).Combination of AZGP1, CEA and CA19-9 had improved diagnosis value accuracy with 74.2% sensitivity and 72.5% specificity.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200000, China. sjtuyingmingxue@163.com.

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.

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AZGP1 overexpression in colon tumorous tissues validated by TMA analysis.(A) Negative AZGP1 expression in normal colonic epithelium; (B) Strong AZGP1 staining in well-differentiated colon tumor tissues; (C) moderately differentiated colon tumor tissues and (D) poorly differentiated colon tumors tissues. Magnification ×200.
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ijms-16-00691-f004: AZGP1 overexpression in colon tumorous tissues validated by TMA analysis.(A) Negative AZGP1 expression in normal colonic epithelium; (B) Strong AZGP1 staining in well-differentiated colon tumor tissues; (C) moderately differentiated colon tumor tissues and (D) poorly differentiated colon tumors tissues. Magnification ×200.

Mentions: Tissue microarray containing 190 samples of primary colon cancer tissues paired with normal colonic tissues was used to determine AZGP1 expression by immunohistochemistry. As shown in Figure 4, AZGP1 protein was localized in the cytoplasm of cancer cells. Although AZGP1 protein was detected in the normal mucosa, the expression was very weak. 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) (Figure 4). Additionally, we evaluated the association between AZGP1 expression and clinicopathological factors as summarized in Table 1. AZGP1 expression was positively associated with AJCC clinical stage (p = 0.024), T classification (p = 0.012), and lymph node metastasis (p = 0.005) (Table 1).


Zinc-α-2-glycoprotein: a candidate biomarker for colon cancer diagnosis in Chinese population.

Xue Y, Yu F, Yan D, Cui F, Tang H, Wang X, Chen J, Lu H, Zhao S, Peng Z - Int J Mol Sci (2014)

AZGP1 overexpression in colon tumorous tissues validated by TMA analysis.(A) Negative AZGP1 expression in normal colonic epithelium; (B) Strong AZGP1 staining in well-differentiated colon tumor tissues; (C) moderately differentiated colon tumor tissues and (D) poorly differentiated colon tumors tissues. Magnification ×200.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307269&req=5

ijms-16-00691-f004: AZGP1 overexpression in colon tumorous tissues validated by TMA analysis.(A) Negative AZGP1 expression in normal colonic epithelium; (B) Strong AZGP1 staining in well-differentiated colon tumor tissues; (C) moderately differentiated colon tumor tissues and (D) poorly differentiated colon tumors tissues. Magnification ×200.
Mentions: Tissue microarray containing 190 samples of primary colon cancer tissues paired with normal colonic tissues was used to determine AZGP1 expression by immunohistochemistry. As shown in Figure 4, AZGP1 protein was localized in the cytoplasm of cancer cells. Although AZGP1 protein was detected in the normal mucosa, the expression was very weak. 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) (Figure 4). Additionally, we evaluated the association between AZGP1 expression and clinicopathological factors as summarized in Table 1. AZGP1 expression was positively associated with AJCC clinical stage (p = 0.024), T classification (p = 0.012), and lymph node metastasis (p = 0.005) (Table 1).

Bottom Line: Zinc-α-2-glycoprotein (AZGP1) is a 41-kDa secreted glycoprotein, which has been detected in several malignancies.In contrast, there was a weakly positive staining in 29.5% (56 of 190) of the normal colonic tissue samples (p < 0.001).Combination of AZGP1, CEA and CA19-9 had improved diagnosis value accuracy with 74.2% sensitivity and 72.5% specificity.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200000, China. sjtuyingmingxue@163.com.

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.

Show MeSH
Related in: MedlinePlus