Department of Surgery, Postgraduate School of Medicine, Gyeongnam Regional Cancer Center, Gyeongsang National University, Jinju, Republic of Korea.
Int J Oncol. 2013 May;42(5):1569-77. doi: 10.3892/ijo.2013.1867. Epub 2013 Mar 27.
F-actin capping protein α1 subunit (CAPZA1) was previously identified in a proteomic analysis of human gastric cancer clinical specimens and selected for further study. The association between CAPZA1 overexpression, detected by immunohistochemistry, and clinicopathological features including survival were evaluated. In vitro gain-of-function and loss-of-function approaches were utilized to assess the function of CPAZA1 in malignancy. Univariate analysis revealed that poorly differentiated disease, according to the World Health Organization (WHO) classification, advanced T stage, positive lymph nodes, high TNM stage, D2 lymph node dissection, adjuvant chemotherapy and CAPZA1 underexpression were significantly associated with cancer-related death (p<0.05); however, only high TNM stage remained significantly associated by multivariate analysis (p<0.01). CAPZA1 overexpression was associated with well differentiated histology, smaller tumor size, lower T stage, absence of lymph node metastasis, lower TNM stage, lower recurrence rate and longer survival time, compared to CAPZA1 underexpression. In vitro, forced expression of CAPZA1 caused a significant decrease in gastric cancer cell migration and invasion, whereas CAPZA1 depletion had the opposite effect. The present study suggests that CAPZA1 could be a marker of good prognosis in gastric cancer and shows that CAPZA1 is associated with decreased cancer cell migration and invasion.
F-肌动蛋白结合蛋白α1 亚基(CAPZA1)在人类胃癌临床标本的蛋白质组学分析中被鉴定出来,并被选中进行进一步研究。通过免疫组织化学检测 CAPZA1 的过表达,并评估其与临床病理特征(包括生存)的相关性。利用体外功能获得和功能丧失方法来评估 CAPZA1 在恶性肿瘤中的功能。单因素分析显示,根据世界卫生组织(WHO)分类,低分化疾病、T 期较晚、阳性淋巴结、高 TNM 分期、D2 淋巴结清扫术、辅助化疗和 CAPZA1 低表达与癌症相关死亡显著相关(p<0.05);然而,多因素分析仅显示高 TNM 分期仍然显著相关(p<0.01)。与 CAPZA1 低表达相比,CAPZA1 过表达与分化良好的组织学、较小的肿瘤大小、较低的 T 分期、无淋巴结转移、较低的 TNM 分期、较低的复发率和更长的生存时间相关。在体外,CAPZA1 的强制表达导致胃癌细胞迁移和侵袭显著减少,而 CAPZA1 的耗竭则产生相反的效果。本研究表明,CAPZA1 可能是胃癌预后良好的标志物,并表明 CAPZA1 与降低癌细胞迁移和侵袭有关。