Abstract
REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.
Highlights
Esophageal cancer occurs worldwide with a variable geographic distribution and ranks 6th in order of incidence and 5th as the leading cause of cancer mortality, affecting men more than women (Jemal et al, 2011)
Thirty paired esophageal squamous cell carcinoma (ESCC) tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting
Immunohistochemical results revealed that REPS2 protein was obviously lower in ESCC tissues compared with adjacent non-cancerous tissues and normal esophageal tissues
Summary
Esophageal cancer occurs worldwide with a variable geographic distribution and ranks 6th in order of incidence and 5th as the leading cause of cancer mortality, affecting men more than women (Jemal et al, 2011). The incidence and the mortality rates of esophageal cancer have been steadily decreasing during the past several decades in China, whereas esophageal cancer is continuing its march as the fastest growing malignancy in the western world. REPS2 ( known as POB1) was initially identified in a yeast two-hybrid screening as a partner of RalBP1, a molecule in the Ras/Ral signaling pathway (Ikeda et al, 1998). This gene is located on the human X chromosome at Xp22 and it has an EH domain in its N-terminal region and two proline-rich motifs and a coiled-coil structure in its C-terminal region. The two proline-rich regions of REPS2 have been shown to interact with the growth factor receptor adaptor protein Grb (Ikeda et al, 1998) and the paxillin-associated protein PAG2 (Oshiro et al, 2002), while the EH domain of REPS2 is found to bind directly to Epsin and Eps (Chen et al, 1998; Morinaka et al, 1999; Kariya et al, 2000)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
