Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma
Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma
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DOI：
10.1007/s00428-004-0982-8
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发表时间：
2004-04-01
期刊：
影响因子：
3.5
通讯作者：
Yasui, W
中科院分区：
文献类型：
--
作者：
Ito, R;Nakayama, H;Yasui, W
Cbl蛋白作为泛素连接酶和多适配器蛋白在下调生长因子受体中发挥重要作用。配体诱导的表皮生长因子受体（EGFR）脱敏已被证明是由Cbl控制的。在本研究中，我们检测了Cbl在胃癌中的表达，并研究了Cbl表达与临床病理特征以及EGFR表达的相关性。67%（82/122）胃癌组织表达Cbl蛋白，29%（35/122）胃癌组织弥漫表达Cbl蛋白。晚期患者弥漫表达Cbl的发生率（28/ 70,40%）明显高于早期患者（7/ 52,14%）（P=0.0010）。Cbl的弥漫性表达与肿瘤细胞在淋巴结的转移有显著相关性（P=0.0318）。EGFR弥漫性表达与浸润深度（P=0.0057）、淋巴结转移（P=0.0371）和肿瘤分期（P=0.0278）相关。随着Cbl表达程度的增强，弥漫性EGFR表达的病例增多，呈显著正相关（P=0.049）。所有Cbl和EGFR弥漫性表达的病例均有淋巴结转移，处于晚期。Cbl、EGFR同步弥漫性表达患者的预后明显差于Cbl、局灶性或EGFR阴性患者（P=0.0086）。转化生长因子- α对胃癌细胞株Cbl蛋白表达有明显的诱导作用。这些结果提示，与EGFR系统相关的Cbl可能与胃癌的发生、侵袭和转移有关。Cbl可能作为侵袭性胃癌的一种新的分子标志物。
Cbl proteins play important roles in downregulation of growth factor receptors by acting as ubiquitin ligases and multi-adapter proteins. Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) has been shown to be controlled by Cbl. In the present study, we examined the expression of Cbl in gastric carcinomas and studied the correlation of Cbl expression with clinicopathological characteristics as well as EGFR expression. Cbl protein was expressed in 67% (82/122) of gastric carcinomas, and diffuse expression of Cbl was detected in 29% (35/122) of the cases. The incidence of cases with diffuse expression of Cbl was significantly higher in advanced cases (28/70, 40%) than in early cases (7/52, 14%) (P=0.0010). Diffuse expression of Cbl was significantly associated with metastasis of tumor cells in lymph nodes (P=0.0318). Diffuse expression of EGFR was significantly associated with depth of invasion (P=0.0057), lymph-node metastasis (P=0.0371) and tumor stages (P=0.0278). As the grades of Cbl expression became stronger, the cases with diffuse EGFR expression increased, the positive correlation being significant (P=0.049). All the cases with diffuse expression of Cbl and EGFR were found to show nodal metastasis and to be at an advanced stage. Moreover, the prognosis of the patients with synchronous diffuse expression of Cbl and EGFR was significantly poorer than that of the patients negative for Cbl and focal or negative for EGFR (P=0.0086). The expression of Cbl protein was clearly induced in gastric carcinoma cell lines by transforming growth factor-alpha treatment. These results suggest that Cbl in connection with the EGFR system may be associated with stomach carcinogenesis, invasion and metastasis. Cbl may serve as a novel molecular marker for aggressive gastric carcinoma.