Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients

Abstract

RASSF2 has recently been identified as a potential tumor suppressor that serves as a Ras effector in various types of human cancers. However, there have been few reports detailing this in gastric cancer. Samples of gastric adenocarcinoma from 276 Chinese patients with follow-up were analyzed for RASSF2 protein expression by immunohistochemistry. RASSF2 was expressed in up to 31.2% (86/276) of this group of gastric carcinoma. The expression of RASSF2 was significantly lower in carcinomas than in normal mucosas (P<0.05). RASSF2 corresponded positively with patient age, histological differentiation, depth of tumor invasion, regional lymph node and distant metastasis, and TNM stage (all P<0.05). Further multivariate analysis revealed that patient gender, depth of tumor invasion, distant metastasis, TNM stage and the expression of RASSF2 were independent prognostic factors for patients with gastric cancer. The Kaplan-Meier plot showed that the overall mean survival time of the patients with RASSF2-negative expression was shorter than that of patients with positive expression (χ(2)=156.874, P<0.0001). Moreover, RASSF2-negative expression had a much more significant effect on the survival of those patients with early stage tumors (χ(2)=127.167, P<0.0001), highlighted by a >50.9% reduction in 3-year survival compared to that of patients with RASSF2-positive expression. In late stages, the difference was also significant (χ(2)=6.246, P=0.019), with a 35.5% reduction in 3-year survival. It is suggested that RASSF2 plays an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for its prognosis.

Figure 1.

Immunohistochemical staining for RASSF2 in gastric cancer lesions and non-cancerous tissues. (A) RASSF2 was positively expressed in non-cancerous tissues; (B) RASSF2 was also positively detected in intestinal metaplasia cells; (C) RASSF2 was negatively or weakly expressed in tubular adenocarcinoma; (D) RASSF2 staining was negative in Signet ring cell carcinoma. Magnification, x200.

Figure 1.

Immunohistochemical staining for RASSF2 in gastric cancer lesions and non-cancerous tissues. (A) RASSF2 was positively expressed in non-cancerous tissues; (B) RASSF2 was also positively detected in intestinal metaplasia cells; (C) RASSF2 was negatively or weakly expressed in tubular adenocarcinoma; (D) RASSF2 staining was negative in Signet ring cell carcinoma. Magnification, x200.

Figure 1.

Immunohistochemical staining for RASSF2 in gastric cancer lesions and non-cancerous tissues. (A) RASSF2 was positively expressed in non-cancerous tissues; (B) RASSF2 was also positively detected in intestinal metaplasia cells; (C) RASSF2 was negatively or weakly expressed in tubular adenocarcinoma; (D) RASSF2 staining was negative in Signet ring cell carcinoma. Magnification, x200.

Figure 1.

Immunohistochemical staining for RASSF2 in gastric cancer lesions and non-cancerous tissues. (A) RASSF2 was positively expressed in non-cancerous tissues; (B) RASSF2 was also positively detected in intestinal metaplasia cells; (C) RASSF2 was negatively or weakly expressed in tubular adenocarcinoma; (D) RASSF2 staining was negative in Signet ring cell carcinoma. Magnification, x200.

Figure 2.

Kaplan-Meier curves with univariate analyses (log-rank) for patients with tumors with RASSF2-negative expression vs. RASSF2-positive expression for all gastric cancer cases. The cumulative 1- and 3-year survival rate was 97.3 and 89.3%, respectively, in the positive RASSF2 protein expression group, but only 79.5 and 14.2% in the negative expression group (χ²=156.874, P<0.0001).