Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood

Abstract

Identification of an isolated tumour cell with metastatic ability is important for predicting the recurrence and prognosis of gastric cancer. A biological marker for evaluating the metastatic ability of gastric cancer cells has not yet been identified. We assessed vascular endothelial growth factor receptor-1 mRNA expression by quantitative real-time reverse transcriptase-polymerase chain reaction. Vascular endothelial growth factor receptor-1 mRNA in peripheral blood was more highly expressed in perioperative metastasis-positive and postoperative recurrence cases than in normal control cases, early cancer cases and nonmetastatic advanced cancer cases. The peripheral blood vascular endothelial growth factor receptor-1 mRNA-positive group was associated with advanced clinical stage, deep invasion beyond the muscularis propria, lymphatic involvement, vascular involvement, lymph node metastasis, positive peritoneal lavage cytology, preoperative metastasis and postoperative recurrence. Flow cytometry analysis disclosed that vascular endothelial growth factor receptor-1 expressing cells in the peripheral blood were more abundant in cancer cases with metastases than in cases without metastases. Our data suggest that the amount of positive cells may provide information on the clinical features of gastric cancer, especially in regard to gastric cancer metastasis.

Figure 1

VEGFR1 mRNA expression in peripheral blood from gastric cancer cases. Group 1 consisted of noncancer patients (n=16). Group 2 consisted of early cancer patients, with tumours that invaded less than the sub-mucosal layer (n=30). Group 3 consisted of advanced cancer patients, where there was evidence of deep invasion beyond the muscularis propria and no preoperative distant metastasis (n=30). Group 4 was the metastasis and recurrence patient group, where there were distant metastases at the time of operation (i.e., liver and/or lung metastasis, peritoneal dissemination) and who developed postoperative recurrence (e.g., peritoneal dissemination and distant metastasis) (n=30). The mean expression level of VEGFR1 mRNA in group 4 was significantly higher than all other groups (P<0.0001, respectively).

Figure 2

VEGFR1 expression with or without metastasis and recurrence. There is no significant difference between patients with metastasis at the time of operation and patients with postoperative recurrence. The higher VEGFR1 expression was observed in patients with metastasis pre- and postoperatively in comparison with gastric cancer patients without metastasis (P<0.0001, respectively).

Figure 3

VEGFR1 expression in blood of gastric cancer cases with or without metastasis. The number of VEGFR1-positive cells in a representative gastric cancer case with metastasis was more abundant (9.8%) than a case without metastasis (2.5%). Particularly, VEGFR1-positive cells in the fraction of monocytes in FS/SS plots were more abundant than those cells in the fraction of lymphoid cells.