Wnt3 gene expression promotes tumor progression in non-small cell lung cancer
Wnt3 gene expression promotes tumor progression in non-small cell lung cancer
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DOI：
10.1016/j.lungcan.2011.10.007
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发表时间：
2012-05-01
期刊：
影响因子：
5.3
通讯作者：
Yokomise, Hiroyasu
中科院分区：
文献类型：
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作者：
Nakashima, Nariyasu;Liu, Dage;Yokomise, Hiroyasu
Wnt基因家族编码多种功能的信号糖蛋白，调节包括肿瘤发生在内的各种正常和病理过程。我们研究了Wnt3基因表达与其靶基因c-Myc和survivin在非小细胞肺癌（NSCLC）患者中的临床意义。128例接受非小细胞肺癌切除术的患者进行了分析。采用定量逆转录聚合酶链反应（RT-PCR）检测Wnt3、c-Myc和survivin基因的表达。免疫组化检测Wnt3、c-Myc和survivin蛋白的表达。TUNEL法测定Ki-67增殖指数和细胞凋亡指数。24例（18.8%）为高wnt3肿瘤。高wnt3肿瘤在鳞状细胞癌中明显多于腺癌（P = 0.0022）。Wnt3基因表达与c-Myc （P = 0.0103）和survivin基因表达显著相关（P = 0.0009）。结果表明，高wnt3肿瘤的Ki-67增殖指数明显高于低wnt3肿瘤（P = 0.0056）。高wnt3肿瘤细胞的凋亡指数明显低于低wnt3肿瘤细胞（P = 0.0245）。高wnt3肿瘤患者的总生存率明显低于低wnt3肿瘤患者（P = 0.0020）。Cox回归分析显示Wnt3状态是NSCLC患者预后的重要因素（危险比2.226,P = 0.0296）。本研究发现Wnt3基因表达与c-Myc和survivin基因表达、肿瘤增殖和肿瘤凋亡显著相关。在NSCLC的进展过程中，Wnt3过表达可能与更具侵袭性的肿瘤的发展有关。2011爱思唯尔爱尔兰有限公司版权所有。
The Wnt gene family encodes the multi-functional signaling glycoproteins regulating various normal and pathological processes including tumorigenesis. We investigated the clinical significance of the Wnt3 gene expression in relation to its target genes, c-Myc and survivin, in patients with non-small cell lung cancer (NSCLC). One hundred and twenty-eight patients who underwent resection of NSCLC were analyzed. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the gene expression of Wnt3, c-Myc, and survivin. Immunohistochemistry was performed to investigate the protein expression of Wnt3, c-Myc, and survivin. The Ki-67 proliferation index and the apoptotic index using the TUNEL method were also evaluated. Twenty-four carcinomas (18.8%) were found to be high-Wnt3 tumors. The high-Wnt3 tumors were significantly more in squamous cell carcinomas than that in adenocarcinomas (P = 0.0022). The Wnt3 gene expression was significantly associated with gene expressions of c-Myc (P = 0.0103) and survivin (P = 0.0009). As a result, the Ki-67 proliferation index was significantly higher in high-Wnt3 tumors than in low-Wnt3 tumors (P = 0.0056). The apoptotic index was significantly lower in high-Wnt3 tumors than in low-Wnt3 tumors (P = 0.0245). The overall survival rate was significantly lower in patients with high-Wnt3 tumors than in those with low-Wnt3 tumors (P = 0.0020). A Cox regression analysis demonstrated that the Wnt3 status was a significant prognostic factor for NSCLC patients (hazard ratio 2.226, P = 0.0296). The present study revealed that Wnt3 gene expression was significantly associated with c-Myc and survivin gene expressions, tumor proliferation, and tumor apoptosis. During the progression of NSCLC, Wnt3 overexpression could be associated with the development of more aggressive tumors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.