Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients.
Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients.
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DOI：
10.3892/or.19.1.203
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发表时间：
2008
期刊：
影响因子：
4.2
通讯作者：
T. Nakashima;Dage Liu;J. Nakano;S. Ishikawa;H. Yokomise;M. Ueno;K. Kadota;Cheng‐long Huang
中科院分区：
文献类型：
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作者：
T. Nakashima;Dage Liu;J. Nakano;S. Ishikawa;H. Yokomise;M. Ueno;K. Kadota;Cheng‐long Huang
Wnt家族基因编码多功能信号糖蛋白，参与多种正常和病理过程的调节，包括肿瘤发生。为了阐明Wnt1在非小细胞肺癌（NSCLC）瘤内表达的临床意义，我们对Wnt1在NSCLC中表达与肿瘤增殖的关系进行了免疫组化研究。瘤内Wnt1蛋白表达呈细胞质染色模式。在研究的151例非小细胞肺癌中，61例（40.4%）为wnt1阳性。肿瘤生物学方面，Wnt1阳性肿瘤的Ki-67增殖指数明显高于Wnt1阴性肿瘤（P=0.0062）。此外，对于调节Wnt增殖的靶点之一c-Myc的表达，wnt1阳性肿瘤细胞中c-Myc阳性的比例显著高于wnt1阴性肿瘤细胞（P=0.0019）。c- myc阳性肿瘤的Ki-67增殖指数明显高于c- myc阴性肿瘤（P=0.0239）。wnt1阳性nsclc患者的总生存率明显低于wnt1阴性nsclc患者（P=0.0003）。Cox回归分析显示，Wnt1状态是NSCLC患者预后的重要因素（危险比1.983；P=0.0061）。我们的研究结果表明，Wnt1过表达影响非小细胞肺癌的肿瘤增殖，部分是通过上调c-Myc。
The Wnt family genes encode multifunctional signaling glycoproteins that are involved in the regulation of a wide variety of normal and pathological processes including tumorigenesis. In order to clarify the clinical significance of the intratumoral Wnt1 expression in non-small cell lung cancer (NSCLC), we performed an immunohistochemical study on the Wnt1 expression in NSCLCs in relation to the tumor proliferation. The intratumoral Wnt1 protein expression appeared in a cytoplasmic staining pattern. Of the 151 NSCLCs studied, 61 carcinomas (40.4%) were Wnt1-positive. Regarding the tumor biology of the intratumoral Wnt1 expression, the Ki-67 proliferation index was significantly higher in Wnt1-positive than in Wnt1-negative tumors (P=0.0062). Furthermore, regarding the expression of c-Myc, one of the proliferation-regulating Wnt targets, the percentage of c-Myc-positive tumor cells was significantly higher in Wnt1-positive than in Wnt1-negative tumors (P=0.0019). The Ki-67 proliferation index was significantly higher in c-Myc-positive than in c-Myc-negative tumors (P=0.0239). The overall survival was significantly lower in patients with Wnt1-positive NSCLCs than in patients with Wnt1-negative NSCLCs (P=0.0003). A Cox regression analysis demonstrated that the Wnt1 status was a significant prognostic factor for NSCLC patients (hazard ratio 1.983; P=0.0061). Our results revealed that the Wnt1 overexpression affects the tumor proliferation in NSCLCs, partly via the upregulation of c-Myc.