RAB27A and RAB27B Expression May Predict Lymph Node Metastasis and Survival in Patients With Gastric Cancer

Abstract

Background/aim: RAB27A and RAB27B are involved in exosome secretion. To date, there have been many attempts to elucidate the roles of RAB27A and RAB27B in the prognosis of various cancer types. The association of RAB27A and RAB27B expression with the clinical and pathological features was evaluated in patients with stomach cancer.

Materials and methods: A total of 360 patients who had undergone surgery for stomach cancer between January 1999 and December 2007 at Gyeongsang National University were enrolled in the study. Disease-free survival (DFS) and disease-specific survival (DSS) were compared according to immunohistochemistry of tumor samples. RAB27A and RAB27B mRNA and protein were also extracted from four stomach cancer cell lines using quantitative polymerase chain reaction and western blotting.

Results: Strong nuclear RAB27A expression in tumor samples was statistically significantly correlated with lymph node metastasis. Cytoplasmic RAB27B expression was related to poor disease-free survival and its combined cytoplasmic and membranous expression was related to disease-specific survival of patients with different histopathological types of stomach cancer. High RAB27A expression and high RAB27B expression was found in four stomach cancer cell blocks. Among the four cell lines, NCI-N87 exhibited the lowest relative mRNA density and HS746T exhibited the highest relative protein density for both RAB27A and RAB27B.

Conclusion: RAB27A and RAB27B expression may help predict lymph node metastasis and survival of patients with gastric cancer.

Keywords: RAB27A; RAB27B; gastric cancer; lymph node metastasis.

Figure 1. Representative images of RAS oncogene family members RAB27A and RAB27B immunostaining patterns. A: Strong and distinct nuclear staining of adenocarcinoma sample with high RAB27A expression. B: Weak nuclear staining of an adenocarcinoma sample with low RAB27A expression. C: Diffuse strong cytoplasmic staining of adenocarcinoma sample with high cytoplasmic RAB27B expression. D: Negative cytoplasmic expression of adenocarcinoma sample with low RAB27B cytoplasmic expression. E: Uniformly intense membranous staining of adenocarcinoma sample with high membranous RAB27B expression. F: Adenocarcinoma sample with low membranous RAB27B expression.

Figure 2. mRNA and protein expression of RAS oncogene family members RAB27A and RAB27B in stomach cancer cell lines MKN-45, NCI-N87, HS746T and SNU-601. A: Total mRNA extracted from human stomach cancer cell lines was used to determine the mRNA levels of RAB27A and RAB27B relative to those of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by quantitative polymerase chain reaction. B: Protein levels of RAB27A and RAB27B in stomach cancer cell lines were determined by western blotting. Data are the mean±standard deviation from three independent experiments.

Figure 3. Expression of RAS oncogene family members RAB27A and RAB27B in cell blocks of four stomach cancer cell lines. Staining considered as high expression for RAB27A was nuclear and strongly positive in all cell blocks of four stomach cancer cell lines. In contrast, high RAB27B expression exhibited weakly positive and cytoplasmic or incomplete membranous staining patterns in all cell blocks of four stomach cancer cell lines.