Expression Of Liver-Intestine Cadherin In Gastric Cancer And Its Implication

Objective:To investigate the expressiom of liver-intestine cadherin(CDH17) in gastric cancer and its association with clinicopathological parameters. To explore the effect of CDH17 upon prognosis in gastric cancer and its role in carcinogenesis and progression of the disease.Methods:(1). CDH17 mRNA expression was detected in 69 cases of gastric cancer and adjacent normal mucosa by real-time polymerase chain reaction(PCR).(2). In the above-mentioned cases, protein levels of CDH17 were analyzed using Western blot.(3). CDH17 protein expression was detected by immunohistochemistry on tissue microarray, which containing 264 samples of primary gastric cancer and the corresponding para-cancerous tissue, and 104 paired lymph node metastases(LNM).(4). kappa tests were used to analyze the association between CDH17 mRNA and protein expression. Chi-square (χ2) tests were used to analyze the association between CDH17 protein expression and clinicopathological data. The effect of CDH17 upon prognosis in gastric cancer was further evaluated using univariate and multivariate Cox regression analyses.Results:(1). In these 69 paired samples.,46 (66.67%) analyzed samples expressed a higher level (at least a 2-fold change) of CDH17 mRNA in gastric cancer tissue specimens than in noncancerous tissue specimens.(2). According to the analysis by western blot, CDH17 protein expression was high in 47 of these cases (47/69,68.12%), which was in agreement with the findings of the qRT-PCR data. The Kappa test showed that there was a correlation between the expression of biglycan mRNA and protein (P= 0.000,к= 0.769).(3). By immunohistochemistry, we found that CDH17 protein was localized in the plasma membrane of gastric cancer cells and CDH17 was up-regulated in gastric cancer compared with paired nomal gastric mucosa(P<0.001). Immnoreactivity of CDH17 was significantly higher in LNM than in primary gastric cancer and normal mucosa(P<0.001).(4). Association between CDH17 protein expression and clinicopathologic factors in gastric cancer:The up-regulation of CDH17 in gastric cancer was correlated with clinical stage(P<0.01), invasion depth(P<0.01), LNM(P<0.01), distant metastasis(P<0.05). Following the developing of UICC stage, the expression of CDH17 protein was increasing subsequently. Among the samples with lymph node metastasis,105 of 148 (70.95%) were positive compared with the samples without lymph node metastasis, of which 62 of 116 samples (53.45%) were positive(P<0.01).(5). Association of CDH17 protein expression with prognosis of patients with gastric cancer: Both overall survival(OS) and disease free survival(DFS) of gastric cancer patients with high expression of CDH17 were decreased significantly during the follow-up period(P<0.01). Positive CDH17 expression was associated with a nearly 5-fold increased risk of distant metastases[hazard ratio(HR) 4.67; 95% confidence interval(CI) 1.76-14.73; P<0.01]. On multivariate analysis, CDH17 was an independent prognostic factor for OS (HR1.97; 95%CI 1.39-4.28; P<0.05)and DFS(HR1.32; 95% CI 0.62-3.25; P<0.05). Tumours with positive CDH17 expression were at greater risk for tumour recurrence in the patients of stageⅡandⅢdisease(P<0.01).Conclusion:The up-regulation of CDH17 in gastric cancer was correlated with clinical stage, invasion depth, LNM, distant metastasis, which showed that CDH17 may participate in tumor invasion and metastasis and play an important role in gastric cancer progression. CDH17 could serve as a biomarker to identify patients of stageⅡand III disease at risk of metastasis or recurrence after gastrectomy, which have important research value for gastric cancer diagnosis, prognosis and treatment.