Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC
Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC
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DOI：
10.1016/j.ejcts.2003.11.031
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发表时间：
2004-03-01
影响因子：
3.4
通讯作者：
Shirakusa, T
中科院分区：
文献类型：
--
作者：
Iwasaki, A;Kuwahara, M;Shirakusa, T
目的：非小细胞肺癌（NSCLC）组织产生许多生长因子，这些生长因子是多功能的，被认为是患者生存的预测因子。本研究旨在评估NSCLC组织中碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、肝细胞生长因子（HGF）的浓度与临床病理因素之间的关系，并确定这些因素是否与长期生存相关。研究方法：我们回顾性研究了71例经组织学证实的肺腺癌或鳞状细胞癌患者，这些患者的主要治疗方法是手术，并且在手术前未接受化疗或放疗。用ELISA法检测71例冰冻组织中bFGF、VEGF、HGF的含量。获得5年和10年生存率以确定长期生存率的最重要预测因素。结果如下：在临床病理学参数中，转移性淋巴结受累病例的组织提取物中bFGF的平均浓度（87.5 +/- 69.3 ng/100 mg蛋白）显著高于无淋巴结受累病例（57.6 +/- 42.5 ng; P < 0.05）。腺癌中VEGF水平（26.8 ± 34.0 ng）高于鳞癌（12.2 ± 13.8 ng; P < 0.05）。HGF水平也显示出组织学差异（14.7 +/- 7.7对10.6 +/- 9.7 ng，P < 0.05）。bFGF蛋白水平基本相同，但在组织学类型方面无统计学显著差异（72.5 +/- 55.2 vs. 63.6 +/- 51.5 ng）。bFGF或VEGF高水平患者的生存率明显低于低水平患者（P = 0.0059; P = 0.0134）。特别是高浓度的bFGF和VEGF与预后显著不良相关（P < 0.0001）。多因素分析表明，淋巴结转移和bFGF和VEGF的水平是独立的预后因素的情况下，非小细胞肺癌（腺癌或鳞状细胞癌）涉及的患者进行了根治性切除术。结论：与肺癌相关的腺癌被认为具有区别于鳞状细胞癌的生物学特征。淋巴结侵袭可能与碱性成纤维细胞生长因子有关。bFGF和VEGF相互促进，并与导致不良预后相关。这项研究的结果表明，有效的治疗，以阻止血管生成可能需要解决至少这两个因素的情况下，非小细胞肺癌。(C)2003 Elsevier B. V.保留所有权利。
Objectives: Non-small cell lung cancer (NSCLC) tissue produces numerous growth factors, which are multifunctional and considered predictive of patient survival. This study sought to evaluate the relationship between concentrations of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) in NSCLC tissue and clinicopathological factors, and determine whether these factors correlate with long-term survival. Methods: We retrospectively investigated 71 patients with histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, for whom the primary curative approach was surgery, and who received no chemotherapy or radiotherapy prior to surgery. bFGF, VEGF, HGF were measured in extracts prepared from these 71 frozen tissue samples by ELISA. Five- and 10-year survival was obtained to determine the most important predictors of long-term survival. Results: Among clinicopathological parameters, the mean concentration of bFGF was significantly higher in tissue extracts from cases involving metastatic nodal involvement (87.5 +/- 69.3 ng/100 mg protein) than in those without nodal involvement (57.6 +/- 42.5 ng; P < 0.05). Levels of VEGF in adenocarcinoma (26.8 +/- 34.0 ng) were higher than for squamous cell carcinoma (12.2 +/- 13.8 ng; P < 0.05). HGF levels also demonstrated histological differences (14.7 +/- 7.7 vs. 10.6 +/- 9.7 ng, P < 0.05). bFGF protein levels were basically the same, but showed no statistically significant differences with respect to histological type (72.5 +/- 55.2 vs. 63.6 +/- 51.5 ng). Patients with high levels of bFGF or VEGF showed significantly worse survival rates than patients with low levels (P = 0.0059; P = 0.0134). In particular, high concentrations of both bFGF and VEGF correlated with markedly poor prognosis (P < 0.0001). Multivariate analysis indicated that lymph node involvement and levels of bFGF and VEGF were independent prognostic factors in cases of NSCLC (adenocarcinoma or squamous cell carcinoma) involving patients who had undergone curative resection. Conclusions: Adenocarcinoma associated with lung cancer is regarded to have biological characteristics that distinguish it from squamous cell carcinoma. Node invasion may be associated with bFGF. bFGF and VEGF augment each other and are associated with leading to poor prognosis. The results of this study suggests that effective therapy to block angiogenesis may need to address at least both of these factors in cases of NSCLC. (C) 2003 Elsevier B.V. All rights reserved.