BACKGROUND Cullin4A (CUL4A), which is a component of E3 ubiquitin ligase, is implicated in many cellular events. Although the altered expression of CUL4A has been reported in several human cancers, the role of CUL4A in esophageal cancer remains unknown. METHODS We investigated the CUL4A expression in primary esophageal squamous cell carcinoma (ESCC) tissue specimens from 120 patients by immunohistochemistry and explored its clinical relevance and prognostic value. Furthermore, the effect of the expression of CUL4A on cancer cell proliferation was analyzed in vitro using an siRNA silencing technique. RESULTS The higher expression of CUL4A was significantly associated with a deeper depth of tumor invasion (P < 0.001) and the presence of venous invasion (P = 0.014). The disease-specific survival (DSS) rate in patients with tumors that showed high CUL4A expression levels was significantly lower than that in patients whose tumors showed low CUL4A expression levels (P = 0.001). Importantly, the CUL4A status was identified as an independent prognostic factor for DSS (P = 0.045). Our results suggested that the CUL4A expression has significant prognostic value in ESCC. Furthermore, CUL4A gene silencing significantly inhibited the proliferation of ESCC cells in vitro. In addition, the knockdown of the CUL4A expression induced G1 phase arrest and increased the p21 and p27 protein levels. CONCLUSIONS CUL4A might play an important role in regulating the proliferation of ESCC cells and promoting the development of postoperative recurrence.

中文翻译：

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Cullin4A的过度表达与食管鳞状细胞癌的不良预后和肿瘤进展有关。

背景技术作为E3泛素连接酶的组成部分的Cullin4A（CUL4A）与许多细胞事件有关。尽管已在几种人类癌症中报道了CUL4A表达的改变，但CUL4A在食道癌中的作用仍然未知。方法采用免疫组织化学方法研究120例原发性食管鳞癌组织样本中CUL4A的表达，探讨其临床意义和预后价值。此外，使用siRNA沉默技术在体外分析了CUL4A表达对癌细胞增殖的影响。结果CUL4A的高表达与更深的肿瘤浸润深度（P <0.001）和静脉浸润（P = 0.014）显着相关。具有高CUL4A表达水平的肿瘤患者的疾病特异性生存（DSS）率显着低于具有低CUL4A表达水平的肿瘤患者的疾病特异性存活率（P = 0.001）。重要的是，CUL4A的状态被确定为DSS的独立预后因素（P = 0.045）。我们的结果表明，CUL4A表达在ESCC中具有重要的预后价值。此外，CUL4A基因沉默在体外显着抑制了ESCC细胞的增殖。此外，CUL4A表达的降低导致G1期阻滞并增加p21和p27蛋白水平。结论CUL4A可能在调节ESCC细胞增殖和促进术后复发发展中起重要作用。