Ring box protein-1 is associated with a poor prognosis and tumor progression in esophageal cancer.

Abstract

Ring box protein-1 (RBX1) is an essential component of the S-phase kinase-associated protein, Cullin and F-box containing ubiquitin ligases. Overexpression of RBX1 has been reported in several cancer types; however, little is known regarding the prognostic value and role of RBX1 in esophageal cancer. The present study examined 120 patients with esophageal cancer (EC) who underwent curative esophagectomy and 61 patients with EC who underwent neoadjuvant combination chemotherapy with docetaxel, cisplatin and 5-fluorouracil (5-FU; DCF) using immunohistochemistry. All specimens were classified into two groups according to the percentage of RBX1-positive tumor cells. In addition, the impact of RBX1 expression on cancer cell proliferation was analyzed in vitro using a small interfering RNA silencing technique. RBX1 expression levels showed significant differences according to tumor size (P<0.001), tumor depth (P=0.002), lymph node metastasis (P=0.004), pathological stage (P=0.001), lymphatic invasion (P=0.001) and venous invasion (P=0.001). The overall survival (OS) rate in the RBX1 high expression group was significantly lower compared with that in the low group (P=0.004). Multivariate analysis demonstrated that RBX1 status was an independent prognostic factor. RBX1 gene silencing inhibited the proliferation of human EC cells and enhanced the antitumor effect of 5-FU. Among patients who underwent neoadjuvant DCF therapy, the RBX1 high expression group had a significantly lower OS rate compared with that of the RBX1-low group (P<0.001). In conclusion, RBX1 has notable prognostic value, and RBX1 may serve an important function in the tumor progression of EC.