Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma.
Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma.
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DOI：
10.3892/ijo.26.6.1517
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发表时间：
2005-06
影响因子：
5.2
通讯作者：
M. Nishi;Y. Abe;Y. Tomii;H. Tsukamoto;H. Kijima;H. Yamazaki;Y. Ohnishi;M. Iwasaki;H. Inoue;Y. Ueyama;Masato Nakamura
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文献类型：
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作者：
M. Nishi;Y. Abe;Y. Tomii;H. Tsukamoto;H. Kijima;H. Yamazaki;Y. Ohnishi;M. Iwasaki;H. Inoue;Y. Ueyama;Masato Nakamura
血管内皮生长因子A（VEGF-A）根据细胞结合结构域的不同有两种亚型。VEGF 189是最大的分子，具有最强的细胞结合能力，并且被认为在各种癌症中对血管形成最有效。本研究旨在明确VEGF 189在肺腺癌中的临床病理特征。采用实时荧光定量聚合酶链反应技术对100例手术切除的肺腺癌组织中VEGF-A亚型（VEGF 121、VEGF 165和VEGF 189）的表达进行了定量检测。分析VEGF亚型的表达情况，包括间质血管化、血管受累、远处转移、淋巴结转移、术后复发时间及长期观察期的预后等临床病理特征。肺腺癌VEGF-A均呈明显阳性表达。22例VEGF-A过表达的腺癌患者术后复发早，5 ~ 15年预后差（P = 0.0093和P = 0.0240，Kaplan Meier，log-rank检验）。VEGF 189在13%的肺腺癌中表达增高。与其他87例相比，这13例VEGF 189表达增加的病例显示出更高的远处转移、更早的术后复发和更差的预后（p = 0.0006，Fisher检验; p = 0.0016和p = 0.0084，Kaplan Meier，对数秩检验）。13例VEGF 189过表达的肺癌还显示血管计数、面积增加（p = 0.0091和p < 0.0001，Mann-Whitney U检验）和静脉受累增强（p = 0.0056，Fisher检验）。细胞结合亚型VEGF 189赋予肺腺癌患者较差的预后，通过血流进行远处转移。
Vascular endothelial growth factor A (VEGF-A) has two kinds of isoforms depending on cellular binding domains. VEGF189 is the largest molecule with the strongest cellular binding ability, and is thought to be most potent for vascularization in various cancers. This study aims to clear the clinicopathological characteristics of VEGF189 in the pulmonary adenocarcinoma. We finely and quantitatively examined the expression of VEGF-A isoforms (VEGF121, VEGF165 and VEGF189) by real-time polymerase chain reaction in a total of 100 pulmonary adenocarcinomas resected by surgical operation. The VEGF isoform expression status was analyzed on clinicopathological features including stromal vascularization, vascular involvement, distant metastasis, lymph nodal metastasis, postoperative relapse time and prognosis of long-term observation periods. All the pulmonary adenocarcinomas showed significant expression of VEGF-A. Twenty-two cases with the adenocarcinomas overexpressing VEGF-A significantly showed earlier postoperative relapse and poorer prognosis between 5- to 15-year periods (p = 0.0093 and p = 0.0240, Kaplan Meier, log-rank test). The expression levels of VEGF189 increased in 13% of the pulmonary adenocarcinoma. These 13 cases with increased VEGF189 expression significantly showed higher distant metastases, earlier postoperative relapse, and poorer prognosis (p = 0.0006, Fisher's test; p = 0.0016 and p = 0.0084, Kaplan Meier, log-rank test) than the other 87 cases. The 13 lung cancers with VEGF189 overexpression also showed increased vessel counts, areas (p = 0.0091 and p < 0.0001, Mann-Whitney U test) and enhanced venous involvement (p = 0.0056, Fisher's test). The cellular binding isoform VEGF189 confers pulmonary adenocarcinoma patients with poorer prognosis with distant metastasis via blood flow.