Abstract
Background2-Zinc-glycoprotein 1 (AZGP1) is a multidisciplinary protein that participates in many important functions in the human body, including fertilization, immunoregulation and lipid mobilization. Recently, it has been shown that AZGP1 is also involved in carcinogenesis and tumor differentiation. In this study, we investigated the expression levels and prognostic value of AZGP1 in primary gastric cancers.Methods and ResultsWe examined the expression of AZGP1 in 35 paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative RT-PCR (qRT-PCR) and western blotting. Furthermore, we analyzed AZGP1 expression in 248 patients who underwent resection procedures between 2005 and 2007 using immunohistochemistry. The relationships between the AZGP1 expression levels, the clinicopathological factors, and patient survival were investigated. AZGP1 expression was significantly reduced at both the mRNA (P = 0.023) and protein levels (P = 0.019) in tumor tissue samples, compared with expression in matched adjacent non-tumor tissue samples. The immunohistochemical staining data showed that AZGP1 expression was significantly decreased in 52.8% (131/248) of gastric adenocarcinoma cases. Clinicopathological analysis showed that the reduced expression of AZGP1 was significantly correlated with tumor location (P = 0.011), histological grade (P = 0.005) and T stage (P = 0.008). Kaplan–Meier survival curves revealed that the reduced expression of AZGP1 was associated with a poor prognosis in gastric adenocarcinoma patients (P = 0.009). Multivariate Cox analysis identified AZGP1 expression was an independent prognostic factor for overall survival of gastric adenocarcinoma patients (HR = 1.681, 95% CI = 1.134–2.494, P = 0.011).ConclusionsOur study suggests that AZGP1 might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis.
Highlights
Gastric cancer is the second most common cause of cancerrelated mortality worldwide, with 988,000 new cases and 736,000 deaths per year [1,2]
Our study suggests that AZGP1 might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis
We identified the relationship between AZGP1 expression and the clinicopathological features of gastric cancer, and we evaluated the prognostic value of AZGP1 expression for the post-resection survival of gastric cancer patients
Summary
Gastric cancer is the second most common cause of cancerrelated mortality worldwide, with 988,000 new cases and 736,000 deaths per year [1,2]. In China, gastric cancer was predicted to be the third most common cancer in 2005 with 0.4 million new cases and 0.3 million deaths reported [3]. The treatment of gastric cancer includes a combination of surgery, chemotherapy, and radiation therapy. Nearly 60% of affected patients succumb to gastric cancer after a curative resection alone or after a curative resection with subsequent adjuvant therapy [4]. Gastric cancer is a heterogeneous disease in both histology and genetics; patient outcome is difficult to predict using classic histological classifications. Several new oncogenes and tumor suppressor genes associated with gastric cancer have been identified. It is clinically important to find efficient new targets for the early diagnosis and effective treatment of gastric cancer
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