Prognostic impact of platelet-derived growth factors in non-small cell lung cancer tumor and stromal cells
Prognostic impact of platelet-derived growth factors in non-small cell lung cancer tumor and stromal cells
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DOI：
10.1097/jto.0b013e3181834f52
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发表时间：
2008-09-01
影响因子：
20.4
通讯作者：
Bremnes, Roy M.
中科院分区：
文献类型：
--
作者：
Donnem, Tom;Al-Saad, Samer;Bremnes, Roy M.
背景：在肿瘤血管生成中，内皮细胞之间存在复杂的相互作用。基质和肿瘤细胞（肿瘤上皮细胞）。血小板源性生长因子（PDGFs）和受体（PDGFRs）是这种相互作用的关键，也是新型抗血管生成疗法的重要靶点。本研究探讨了这些分子标记物在肿瘤细胞和肿瘤间质的切除的非小细胞肺癌（NSCLC）tumors.Methods：肿瘤组织标本从335例切除的I至IIIA期NSCLC患者和组织芯片构建从重复核心的肿瘤细胞和肿瘤相关的基质从每个标本。免疫组化用于评估分子标志物PDGF-A、-B、-C和-D以及PDGFR-α和-beta.Results的表达：在单变量分析中，肿瘤细胞高表达PDGF-B（p = 0.001）。PDGF-C（p = 0.01）和PDGFR-α（p = 0.026）是疾病特异性生存的阴性预后指标。在肿瘤间质中，PDGF-A（p = 0.009）、PDGF-B（p = 0.04）、PDGF-D（p = 0.019）和PDGFR-α（p = 0.019）的高表达与良好预后相关。在多变量分析中，高肿瘤细胞PDGF-B（p = 0.001）和PDGFR-α（p = 0.047）表达是疾病特异性存活的独立负预后因素，而在基质细胞中，高PDGF-A（p = 0.001）表达具有所有独立的正存活影响。我们的结果表明PDGF-B和PDGFR-α抑制是NSCLC治疗中一种有趣的方法，但也证明了理解内皮、基质、和肿瘤细胞。
Background: In tumor angiogenesis there is a complex interplay between endothelial. stromal, and tumor cells (neoplastic epithelial cells). Platelet-derived growth factors (PDGFs) and receptors (PDGFRs) are pivotal in this interaction, and important targets in novel antiangiogenic therapies. This Study investigates the prognostic impact of these molecular markers in tumor cells and tumor stroma of resected non-small cell lung cancer (NSCLC) tumors.Methods: Tumor tissue samples from 335 resected patients with stage I to IIIA NSCLC were obtained and tissue microarrays were constructed from duplicate cores Of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the Molecular markers PDGF-A, -B, -C, and -D and PDGFR-alpha and -beta.Results: In univariate analyses, high tumor cell expression of PDGF-B (p = 0.001). PDGF-C (p = 0.01), and PDGFR-alpha (p = 0.026) were negative prognostic indicators for disease-specific survival. In tumor stroma, high expression of PDGF-A (p = 0.009) PDGF-B (p = 0.04), PDGF-D (p = 0.019), and PDGFR-alpha (p = 0.019) correlated with good prognosis. In multivariate analyses, high tumor cell PDGF-B (p = 0.001) and PDGFR-alpha (p = 0.047) expression were independent negative prognostic factors for disease-specific survival, whereas in stromal cells high PDGF-A) = 0.001) expression had ail independent positive survival impact.Conclusion: Our results indicate PDGF-B and PDGFR-alpha inhibition as an interesting approach in NSCLC treatment, but also demonstrates the importance of understanding the Cellular crosstalk between endothelial, stromal, and tumor cells when targeting PDGF markers.