He Jian-Zhong, Wu Zhi-Yong, Wang Shao-Hong, Ji Xia, Yang Cui-Xia, Xu Xiu-E, Liao Lian-Di, Wu Jian-Yi, Li En-Min, Zhang Kai, Xu Li-Yan
The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou 515041, Guangdong, PR China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, PR China.
Department of Oncology Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou 515041, Guangdong, PR China.
Hum Pathol. 2017 Aug;66:115-125. doi: 10.1016/j.humpath.2017.06.003. Epub 2017 Jun 9.
Our previous studies have highlighted the importance of ezrin in esophageal squamous cell carcinoma (ESCC). Here our objective was to explore the clinical significance of ezrin-interacting proteins, which would provide a theoretical basis for understanding the function of ezrin and potential therapeutic targets for ESCC. We used affinity purification and mass spectrometry to identify PDIA3, CNPY2, and STMN1 as potential ezrin-interacting proteins. Confocal microscopy and coimmunoprecipitation analysis further confirmed the colocalization and interaction of ezrin with PDIA3, CNPY2, and STMN1. Tissue microarray data of ESCC samples (n=263) showed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower for the CNPY2 (OS, P=.003; DFS, P=.011) and STMN1 (OS, P=.010; DFS, P=.002) high-expression groups compared with the low-expression groups. By contrast, overexpression of PDIA3 was significantly correlated with favorable survival (OS, P<.001; DFS, P=.001). Cox regression demonstrated the prognostic value of PDIA3, CNPY2, and STMN1 in ESCC. Furthermore, decision tree analysis revealed that the resulting classifier of both ezrin and its interacting proteins could be used to better predict OS and DFS of patients with ESCC. In conclusion, a signature of ezrin-interacting proteins accurately predicts ESCC patient survival or tumor recurrence.
我们之前的研究强调了埃兹蛋白在食管鳞状细胞癌（ESCC）中的重要性。在此，我们的目的是探索与埃兹蛋白相互作用的蛋白质的临床意义，这将为理解埃兹蛋白的功能以及ESCC的潜在治疗靶点提供理论依据。我们使用亲和纯化和质谱法鉴定出PDIA3、CNPY2和STMN1为潜在的与埃兹蛋白相互作用的蛋白质。共聚焦显微镜和免疫共沉淀分析进一步证实了埃兹蛋白与PDIA3、CNPY2和STMN1的共定位及相互作用。ESCC样本（n = 263）的组织芯片数据显示，与低表达组相比，CNPY2高表达组（总生存期，P = .003；无病生存期，P = .011）和STMN1高表达组（总生存期，P = .010；无病生存期，P = .002）的5年总生存期（OS）和无病生存期（DFS）显著更低。相比之下，PDIA3的过表达与良好的生存期显著相关（总生存期，P < .001；无病生存期，P = .001）。Cox回归证明了PDIA3、CNPY2和STMN1在ESCC中的预后价值。此外，决策树分析显示，由埃兹蛋白及其相互作用蛋白组成的分类器可用于更好地预测ESCC患者的总生存期和无病生存期。总之，埃兹蛋白相互作用蛋白特征能准确预测ESCC患者的生存期或肿瘤复发。
