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结直肠癌中 K-ras 突变状态与 VEGFR1、VEGFR2 和 PDGFRalpha 的表达相关。

K-ras mutation status correlates with the expression of VEGFR1, VEGFR2, and PDGFRalpha in colorectal cancer.

机构信息

First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, Mainz 55101, Germany.

出版信息

Int J Colorectal Dis. 2010 Feb;25(2):181-6. doi: 10.1007/s00384-009-0843-7. Epub 2009 Nov 20.

Abstract

AIM

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

目的

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。

方法

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。

结果

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)。

结论

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。

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