Decreased Expression of RASSF6 Is a Novel Independent Prognostic Marker of a Worse Outcome in Gastric Cancer Patients after Curative Surgery

Background. Our previous study observed that the expression of RASSF6, a member of the Ras-association domain family, was down-regulated in gastric cancer cells. The present study further investigated the clinical significance of RASSF6 in gastric cancer. Methods. Using real-time PCR, Western blot analysis, tissue microarray (TMA), and immunohistochemical staining, we evaluated RASSF6 mRNA and protein levels in tumor tissues and in the paired adjacent normal mucosa from patients with gastric cancers at different stages. Results. RASSF6 mRNA and protein levels were decreased in gastric cancer tissues compared with the adjacent normal mucosa. Immunohistochemical detection of RASSF6 in a TMA that contained 264 paired specimens showed that a decreased cytoplasmic RASSF6 expression was significantly associated with the extent of cancer invasion, lymph node metastasis, distant metastasis, tumor histological grade, advanced clinical stage, and Ki-67 proliferative index. Moreover, RASSF6 expression in metastatic lymph nodes was lower than in the paired primary tumors. Patients with RASSF6-negative tumors had extremely higher disease recurrence rates and poorer survival than patients with RASSF6-positive tumors even after radical surgery. Stratification analysis revealed RASSF6 as an independent predictor for tumor recurrence in patients with gastric cancers irrespective of tumor stage. Conclusions. RASSF6 might contribute to the progression of gastric carcinogenesis and may function as a novel independent prognostic marker for the prediction of the recurrence of cancer in patients after curative operations.