Bone morphogenetic protein-2 levels are elevated in the patients with gastric cancer and correlate with disease progression

Bone morphogenetic protein-2 (BMP-2) was reported to enhance migration, invasion, and metastasis at the various types of cancer cells. The purpose of this study is to identify the role of BMP-2 in progression of gastric cancer. Forty-four patients with operable gastric cancer were enrolled. Also, twenty healthy volunteers were enrolled as control group. All patients received gastrectomy with D2 lymphadenectomy, and surgical staging was performed. Whole blood was obtained preoperatively in all patients, and serum BMP-2 levels were quantified by commercially available ELISA kit. Immunohistochemical stain for BMP-2 in all gastric cancer tissues was performed using tissue microarray. All patients showed increased serum BMP-2 levels compared with control group, when upper normal limit was defined as the mean of control serum level + 2 × standard deviation. The mean serum BMP-2 level of lymph node positive group was significantly elevated than that of lymph node-negative group (382.7 pg/ml, 95% CI 341.99-423.4 pg/ml vs 211.69 pg/ml, 95% CI 191.09-232.29 pg/ml, P < 0.001). The serum BMP-2 was strongly correlated with the depth of invasion (T stage) and the extent of regional lymph node involvement (N stage) (r = 0.662, P < 0.001 and r = 0.831, P < 0.001, respectively). Moreover, the serum BMP-2 was correlated with the grade of tumor histology(r = 0.421, P = 0.008). Immunohistochemical stain showed the specific expression of BMP-2 in cancer cells compared with normal gastric mucosa. In conclusion, serum BMP-2 is associated with progression from early localized gastric cancer to locally advanced gastric cancer.