Platelet-Derived Growth Factor Gene Polymorphisms in Patients With Ovarian Cancer

Clinical Ovarian and Other Gynecologic Cancer Pub Date : 2012-06-01 DOI:10.1016/j.cloc.2012.02.020

Christine Vestergaard Madsen , Karina Dahl Steffensen , Marianne Waldstrøm , Rikke Fredslund Andersen , Charlotte Hasselholt Søgaard , Ivan Brandslund , Anders Jakobsen

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引用次数: 2

Abstract

Introduction

New reliable and validated markers are desirable in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system plays an important role in tumor growth and angiogenesis, and high expression of PDGF/PDGF receptor (PDGFR) has been reported in ovarian cancer. Single nucleotide polymorphisms (SNPs) within a gene may be important for the function of the protein. This had led to the hypothesis that SNPs within the PDGF system could have clinical relevance as prognostic biomarkers in ovarian cancer.

Methods

The study included hypothesis-generating patient material from 170 patients with histologically verified epithelial ovarian cancer in which 5 tagging SNPs in the promoter region of the PDGF-AA, PDGF-BB, PDGFR-α, and PDGFR-β genes were analyzed by means of SNaPshot Multiplex (Applied Biosystems, Carlsbad, CA) and sequencing methods. The results were validated in an independent second cohort of 85 patients.

Results

In the hypothesis-generating study, survival analyses were made for all 5 SNPs. PDGF-AA 1589 G/T genotype was found to be associated with overall survival in univariate analysis (P = .03), with a clear trend seen in Cox multivariate analysis (P = .12; hazard ratio, 0.75). However, the suggested prognostic importance of PDGF-AA 1589 G/T was not confirmed in the second cohort.

Conclusion

Tagging SNPs in the promoter region of the PDGF-AA, PDGF-BB, PDGFR-α, and PDGFR-β genes, as evaluated here, are not likely to be of prognostic importance in patients with ovarian cancer.

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卵巢癌患者血小板衍生生长因子基因多态性

新的可靠和有效的标志物是卵巢癌治疗中需要的。血小板衍生生长因子(PDGF)系统在肿瘤生长和血管生成中起重要作用，PDGF/PDGF受体(PDGFR)在卵巢癌中高表达已被报道。基因内的单核苷酸多态性(SNPs)可能对蛋白质的功能很重要。这导致了PDGF系统内的snp可能作为卵巢癌预后生物标志物具有临床相关性的假设。方法采用SNaPshot Multiplex (Applied Biosystems, Carlsbad, CA)和测序方法，对来自170例组织学证实的上皮性卵巢癌患者的假设生成患者材料进行分析，其中PDGF-AA、PDGF-BB、PDGFR-α和PDGFR-β基因启动子区域的5个标记snp进行分析。结果在独立的第二队列85例患者中得到验证。结果在产生假设的研究中，对所有5个snp进行了生存分析。单因素分析发现PDGF-AA 1589 G/T基因型与总生存率相关(P = .03)， Cox多因素分析发现PDGF-AA 1589 G/T基因型与总生存率相关(P = .12;风险比，0.75)。然而，PDGF-AA 1589 G/T的预后重要性在第二队列中未得到证实。结论标记PDGF-AA、PDGF-BB、PDGFR-α和PDGFR-β基因启动子区域的snp对卵巢癌患者的预后不太可能具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Clinical Ovarian and Other Gynecologic Cancer

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