Expression and Clinical Significance of REPS2 in Human Esophageal Squamous Cell Carcinoma

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosisof 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 cellcarcinoma (ESCC).
Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patientoutcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophagealepithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR andWestern blotting.
Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissuesand cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph nodemetastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression wassignificantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially inearly stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patientswith 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 factorfor ESCC patients.
Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute tomalignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target forESCC patients.