Overexpression and cytoplasmic accumulation of Hepl is associated with clinicopathological parameters and poor prognosis in non-small cell lung cancer
Overexpression and cytoplasmic accumulation of Hepl is associated with clinicopathological parameters and poor prognosis in non-small cell lung cancer
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Hepl 的过度表达和细胞质积累与非小细胞肺癌的临床病理参数和不良预后相关
DOI：
10.1007/s13277-012-0517-x
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发表时间：
2013-02-01
期刊：
影响因子：
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通讯作者：
Wang, En-Hua
中科院分区：
文献类型：
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作者：
Miao, Yuan;Wang, Liang;Wang, En-Hua
Hepl于2008年首次描述，是Crk相关底物（CAS）家族的第四个成员，并且在肺中特异性表达。与其他CAS蛋白相比，Hepl对不同细胞类型中的细胞迁移具有不同的影响。我们推测Hepl可能在肺癌的侵袭和转移中起作用。我们定量表达和亚细胞定位的Hep 1在143个非小细胞肺癌（NSCLC）组织，相邻的非癌组织，和8个肺癌细胞系，使用Western印迹，免疫组化和免疫荧光染色。Hepl的表达与NSCLC的临床病理特征有关。72.3%（103/143）的非小细胞肺癌组织中Hep 1过表达，与癌旁肺组织相比差异有统计学意义（P = 0.022）。Hep 1的过表达与淋巴结转移和高TNM分期有关（分别为P = 0.005和P = 0.045）。Kaplan-Meier生存曲线和log-rank检验显示Hepl过表达与NSCLC患者的总生存率相关（P < 0.001），考克斯回归分析显示Hepl过表达是NSCLC患者的独立预后因素。此外，在高转移潜能肺癌细胞系（H1299和BE 1）中观察到Hepl的细胞质积累，但在低转移潜能细胞系（LTE和A549）中未观察到。本研究揭示Hepl在NSCLC细胞核中过度表达，并异常积聚在细胞质中，提示Hepl可能在肺癌的进展中起作用，包括淋巴结转移和TNM分期。此外，Hepl可能是肺癌中有用的预后因子。
Hepl, first described in 2008, is the fourth member of the Crk-associated substrate (CAS) family and is specifically expressed in the lung. Compared to other CAS proteins, Hepl has a varying effect on cell migration in different cell types. We speculated that Hepl may play a role in lung cancer invasion and metastasis. We quantified the expression and subcellular localization of Hepl in 143 non-small cell lung cancer (NSCLC) tissues, adjacent noncancerous tissues, and eight lung cancer cell lines using Western blotting, immunohistochemistry, and immunofluorescent staining. Expression of Hepl was correlated with the clinicopathological features of NSCLC. Hepl was overexpressed in 72.3 % (103/143) of the NSCLC tissues, compared to the adjacent noncancerous lung tissues (P = 0.022). Overexpression of Hepl was associated with lymph node metastasis and high TNM stage (P = 0.005 and P = 0.045, respectively). Kaplan-Meier survival curves and the log-rank test indicated that overexpression of Hepl correlated with poorer overall survival in NSCLC (P < 0.001), and Cox regression analysis demonstrated that overexpression of Hepl was an independent prognostic factor in NSCLC. Furthermore, cytoplasmic accumulation of Hepl was observed in a high metastatic potential lung cancer cell lines (H1299 and BE1), but not in low metastatic potential cell lines (LTE and A549). This study reveals that Hepl is overexpressed in the nucleus and aberrantly accumulates in the cytoplasm of NSCLC cells, and indicates that Hepl may play a role in the progression of lung cancer, including lymph node metastasis and TNM stage. Additionally, Hepl may be a useful prognostic factor in lung cancer.