Ezrin Expression Is an Independent Prognostic Factor in Gastro-intestinal Cancers
Ezrin Expression Is an Independent Prognostic Factor in Gastro-intestinal Cancers
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DOI：
10.1007/s11605-013-2384-1
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发表时间：
2013-12-01
影响因子：
3.2
通讯作者：
Kocher, Hemant M.
中科院分区：
文献类型：
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作者：
Arumugam, Prabhu;Partelli, Stefano;Kocher, Hemant M.
Ezrin是一种细胞膜骨架连接蛋白家族成员，与肿瘤转移有关，我们对手术切除的结直肠癌肝转移灶（CRLM）和乏特壶腹癌（CAV）的全组织切片进行了微阵列分析，以确定Ezrin表达水平及其与生存的相关性。通过体外实验评估ezrin对CAV侵袭能力的需求，结果表明ezrin评分低的CAV 5年生存率高于ezrin评分高的CAV（P < 0.0001）。类似地，在CRLM的侵袭性前沿的高ezrin表达导致差的无病生存率（P = 0.05）。多因素分析显示ezrin高表达是CAV的一个独立的不良预后因素（风险比（HR）15.22）（95%置信区间（CI）1.98-117.03），P < 0.01）和CRLM（HR 6.42（95%CI 1.01-52.43），P = 0.05），在其他临床相关变量中，如淋巴结转移（CAV）和肝外疾病的存在，大的肝转移（> 5 cm），和闭合手术切除边缘（< 5 mm）（均用于CRLM）。体外实验表明，ezrin表达对细胞的粘附和侵袭活动至关重要，在原发性CAV和CRLM中，ezrin高表达提示预后不良。
Ezrin, a member of the ezrin-radixin-moesin (ERM) family of plasma membrane-cytoskeleton linker proteins, has been associated with metastatic behavior.Microarrayed pathological tissues of surgically resected colorectal cancer liver metastasis (CRLM) and whole tissue sections of cancer of the ampulla of Vater (CAV) were analyzed to determine ezrin expression levels and correlation with survival. The requirement of ezrin in invasive capability was assessed using in vitro assays.Surgically resected CAV showing a low ezrin score have a better 5-year disease-specific survival than those showing a high ezrin score (P < 0.0001). Similarly, high ezrin expression at the invasive front of CRLM resulted in poor disease-free survival (P = 0.05). Multivariate analysis demonstrated high ezrin expression to be an independent adverse prognostic factor for CAV (hazard ratio (HR) 15.22 (95 % confidence interval (CI) 1.98-117.03), P < 0.01) and CRLM (HR 6.42 (95 % CI 1.01-52.43), P = 0.05), among other clinically relevant variables such as lymph node metastasis (for CAV) and the presence of extrahepatic disease, large hepatic metastases (> 5 cm), and close surgical resection margins (< 5 mm) (all for CRLM). In vitro experiments indicated that ezrin expression was vital for cellular processes such as adhesive and invasive activity.High ezrin expression indicates an adverse prognosis in primary CAV and CRLM.