First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, Mainz 55101, Germany.
Int J Colorectal Dis. 2010 Feb;25(2):181-6. doi: 10.1007/s00384-009-0843-7. Epub 2009 Nov 20.
We initiated this study in order to analyze whether the expression level of targeted receptor tyrosine kinases (RTK) is associated with the K-ras mutation status.
The expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta, and EGFR1 was analyzed in 93 samples of human colorectal carcinoma samples and correlated with the K-ras mutation status as identified by PCR-RFLP.
VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta, and EGFR1 were expressed at relevant levels in 95%, 46%, 46%, 85%, 62%, and 82%, respectively. K-ras mutations were present in 53% (codon 12, 47%; codon 13, 6%). Expression of VEGFR1 (P = 0.0263), VEGFR2 (P = 0.0466), and PDGFRalpha (P = 0.0063) was significantly linked to K-ras codon 12 or 13 mutation. In addition, co-expression of VEGFR2 and PDGFRalpha was significantly associated with K-ras mutation (P = 0.0145).
Our data reveal that specific RTKs are over-expressed in K-ras mutated cancers. It needs to be addressed in prospective studies whether these patients will benefit from tyrosine kinase inhibitors more than K-ras wild-type.
我们开展本研究旨在分析靶向受体酪氨酸激酶(RTK)的表达水平是否与 K-ras 突变状态相关。
采用 PCR-RFLP 方法检测 93 例人结直肠癌样本的 K-ras 突变状态,并分析这些样本中血管内皮生长因子受体 1(VEGFR1)、血管内皮生长因子受体 2(VEGFR2)、血管内皮生长因子受体 3(VEGFR3)、血小板衍生生长因子受体α(PDGFRα)、血小板衍生生长因子受体β(PDGFRβ)和表皮生长因子受体 1(EGFR1)的表达模式。
VEGFR1、VEGFR2、VEGFR3、PDGFRα、PDGFRβ 和 EGFR1 的表达水平分别为 95%、46%、46%、85%、62%和 82%。K-ras 突变存在于 53%(密码子 12,47%;密码子 13,6%)的样本中。VEGFR1(P=0.0263)、VEGFR2(P=0.0466)和 PDGFRα(P=0.0063)的表达与 K-ras 密码子 12 或 13 突变显著相关。此外,VEGFR2 和 PDGFRα 的共表达与 K-ras 突变显著相关(P=0.0145)。
我们的数据显示,特定的 RTK 在 K-ras 突变型癌症中过度表达。需要在前瞻性研究中解决这些患者是否会比 K-ras 野生型患者从酪氨酸激酶抑制剂中获益更多的问题。