Expression of cellular retinoic acid binding protein 1 predicts peritoneal recurrence of gastric cancer.

Abstract

To improve the outcome of gastric cancer, novel markers that predict postoperative prognosis are required. For this purpose, the function of cellular retinoic acid binding protein 1 (CRABP1) in gastric cancer cells was investigated and it was determined whether it serves as a novel biomarker for gastric cancer. Reverse transcription-quantitative (RT-q) PCR and a PCR-array method were used to determine whether the expression of CRABP1 mRNA in gastric cancer cell lines correlated with the expression of cancer-related genes. The correlations of CRABP1 mRNA expression in tissues with clinicopathological factors of 230 patients who underwent radical gastrectomy were further evaluated. CRABP1 mRNA levels varied among gastric cancer cell lines and showed significant positive correlations with numerous epithelial-mesenchymal transition factors. Additionally, CRABP1 knockdown significantly suppressed the proliferation, migration and invasion of gastric cancer cell lines. In a mouse xenograft model of peritoneal metastasis of gastric cancer, it was found that the total weight of disseminated nodules was lower in the group, in which CRABP1 mRNA levels were knocked down compared with those of the untransfected group. Disease-free survival (DFS) was significantly shorter in patients with high expression of CRABP1, and multivariate analysis of DFS revealed that high expression of CRABP1 in the tumor area and lymph node metastasis served as an independent factor associated with poor prognosis. High expression of CRABP1 in cancer tissues was associated with a greater incidence of peritoneal recurrences after curative gastrectomy. These findings indicated that CRABP1 contributes to the malignant phenotype of gastric cancer cells and may serve as a biomarker for prognosing recurrence after curative resection, particularly peritoneal dissemination.