Expression And Diagnostic Significance Of Dkk1 In Human Gastric Cancer

Background: Gastric cancer is one of the most dangerous threats to human health, its incidence is in the fourth place behind cancers of the lung, breast, colon and rectum, with an estimated 934 000 new cases per year. It is the second most common cause of death from cancer (700 000 deaths annually). Almost 42% of the cases occur in China alone. According to recent researches, the mutation and abnormal expression of components involved in Wnt signaling pathway have been implicated in tumor growth, progression, angiogenesis and metastasis. Secreted protein DKK1 is an important regulator of Wnt signaling pathway, and is abnormal expressed in lung cancer, esophageal adenocarcinoma, liver carcinoma, et al, but the relationship with gastric cancer remains to be identified. So we studied the DKK1 mRNA and DKK1 protein expression levels in gastric cancer tissues, also determined sera DKK1 concentration, which is beneficial to understand molecular mechanism of gastric cancer, also give us reference on its potential value as a clinical serological indicator of diagnosis.Methods: 25 tumor and 15 adjacent non-tumor tissues of stomach were obtained by surgical resection in Affiliated Hospital of Hebei University, between March 2007 and June 2009, and the tissues were resected before malignancies were treated. Serum samples of gastric cancer patients and healthy people were prepared with bloods supplied by Baoding Tumor Hospital and Affiliated Hospital of Hebei University between January 2008 and August 2009, all cancer bloods is collected before surgical removal, chemotherapy or radiation therapy. DKK1 mRNA and DKK1 protein expression levels in gastric cancer tissues were investigated using semi-quantitative RT-PCR and Western blot. Sera DKK1 concentration were determined using ELISA. Differences between groups were tested using SPSS and other biological softwares.Results: According to RT-PCR and Western blot analysis, there were no significant differences in DKK1 mRNA and DKK1 protein expression levels in gastric tumor tissues compared with adjacent non-tumor tissues, but we observed great up- and down-regulation of expression levels of DKK1 in some cancer tissues. Serum concentration of DKK1 were decreased significantly in gastric cancer patients with 4.471μg/L(0.885-23.829μg/L) than healthy donors with 5.015μg/L(1.705-8.384μg/L), P<0.01. At the concentration of 3.5390μg/L, 61.8% gastric cancer serum samples can be differentiated, whereas only 15.8% of healthy volunteers were under this value. So, the diagnostic sensitivity is 61.8%, specificity is 84.2%.Conclusions: The differences of DKK1 mRNA and protein expression between tumor tissues and adjacent non-tumor tissues are not significant, but there was a significant decrease of DKK1 expression level in cancer serum samples compared with normal healthy samples, hint us DKK1 may plays an important role at the early stage of gastric cancer carcinogenesis. The great up- and down-regulation of expression levels of DKK1 mRNA and protein in some cancer tissues clue to that it may be sensitive to histologic subtypes, TNM stage, lymph node metastasis and other pathological variables in patients with gastric cancer. Serum concentration of DKK1 were decreased significantly in gastric cancer patients with diagnostic sensitivity of 61.8% and specificity of 84.2%, approves DKK1 may be an index for diagnosis of gastric cancer.