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与相应的原发性结直肠癌相比,肝转移灶中血管内皮生长因子信使核糖核酸的表达水平得以保留。

Vascular endothelial growth factor messenger RNA expression level is preserved in liver metastases compared with corresponding primary colorectal cancer.

作者信息

Kuramochi Hidekazu, Hayashi Kazuhiko, Uchida Kazumi, Miyakura Satoru, Shimizu Daisuke, Vallböhmer Daniel, Park Seongjin, Danenberg Kathleen D, Takasaki Ken, Danenberg Peter V

机构信息

University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.

出版信息

Clin Cancer Res. 2006 Jan 1;12(1):29-33. doi: 10.1158/1078-0432.CCR-05-1275.

Abstract

PURPOSE

Increased vascular endothelial growth factor (VEGF) expression is associated with colorectal cancer liver metastases. It is reasonable to expect that measurement of VEGF in liver metastases would provide the best prediction of therapy benefit for VEGF-targeted drugs, such as bevacizumab (Avastin). In this study, we evaluated how VEGF mRNA level in primary colorectal cancer was related to that in corresponding liver metastases. Thirty-one pairs of primary colorectal cancer and corresponding liver metastases were analyzed.

EXPERIMENTAL DESIGN

Formalin-fixed, paraffin-embedded tumor specimens were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse transcription. Quantitation of VEGF and internal reference gene (beta-actin) was done using real-time PCR (Taqman PCR).

RESULTS

There was no difference between median VEGF mRNA levels of primary colorectal cancer and liver metastases (median value 3.79 versus 3.97: P = 0.989). On an individual basis, there was a significant correlation in VEGF mRNA expression between primary colorectal cancer and corresponding liver metastases (r(s) = 0.6627, P < 0.0001). In addition, the VEGF mRNA levels of the patients who had two or more liver metastatic tumors were significantly higher than those of the patient who had solitary liver metastatic tumor in both primary cancer (5.02 versus 3.34: P = 0.0483) and liver metastases (4.38 versus 3.25: P = 0.0358).

CONCLUSION

Good prediction of VEGF mRNA levels in liver metastases can be obtained by measuring those of primary colorectal cancer. The risk of multiple liver metastatic tumors might be predictable by measuring VEGF mRNA expression in primary colorectal cancer. Further study is required to confirm these preliminary results.

摘要

目的

血管内皮生长因子(VEGF)表达增加与结直肠癌肝转移相关。可以合理预期,检测肝转移灶中的VEGF水平将为VEGF靶向药物(如贝伐单抗,商品名阿瓦斯汀)的治疗获益提供最佳预测。在本研究中,我们评估了原发性结直肠癌中VEGF mRNA水平与相应肝转移灶中VEGF mRNA水平的关系。分析了31对原发性结直肠癌及其相应的肝转移灶。

实验设计

使用激光捕获显微切割技术从福尔马林固定、石蜡包埋的肿瘤标本中分离组织。提取RNA并通过逆转录制备cDNA。使用实时PCR(Taqman PCR)对VEGF和内参基因(β-肌动蛋白)进行定量分析。

结果

原发性结直肠癌和肝转移灶的VEGF mRNA水平中位数无差异(中位数分别为3.79和3.97:P = 0.989)。就个体而言,原发性结直肠癌与其相应肝转移灶的VEGF mRNA表达存在显著相关性(rs = 0.6627,P < 0.0001)。此外,有两个或更多肝转移瘤的患者,其原发性癌(5.02对3.34:P = 0.0483)和肝转移灶(4.38对3.25:P = 0.0358)中的VEGF mRNA水平均显著高于仅有单个肝转移瘤的患者。

结论

通过检测原发性结直肠癌的VEGF mRNA水平可以很好地预测肝转移灶中的VEGF mRNA水平。通过检测原发性结直肠癌中的VEGF mRNA表达,可能预测多灶性肝转移瘤的风险。需要进一步研究来证实这些初步结果。

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