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血管内皮生长因子189 mRNA亚型的表达与非小细胞肺癌的肿瘤血管生成、患者生存率及术后复发密切相关。

Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer.

作者信息

Yuan A, Yu C J, Kuo S H, Chen W J, Lin F Y, Luh K T, Yang P C, Lee Y C

机构信息

Division of Chest Medicine, Department of Internal Medicine. National Taiwan University hospital and Institute of Biomedical Academia Sinica, Taipei.

出版信息

J Clin Oncol. 2001 Jan 15;19(2):432-41. doi: 10.1200/JCO.2001.19.2.432.

DOI:10.1200/JCO.2001.19.2.432
PMID:11208836
Abstract

PURPOSE

The purpose of this study was to evaluate the correlation between the expression of four different vascular endothelial growth factor (VEGF) mRNA isoforms (VEGF121, VEGF165, VEGF 189, and VEGF206) and the clinicopathologic characteristics, tumor angiogenesis, and outcome of patients with non-small-cell lung cancer.

PATIENTS AND METHODS

We examined the expression of four different VEGF mRNA isoforms in 57 non-small-cell lung cancers using reverse transcriptase polymerase chain reaction and the tumor angiogenesis using immunohistochemical staining.

RESULTS

All 57 lung cancer samples expressed the VEGF121, VEGF165, and VEGF189 mRNA isoforms, and three expressed the VEGF206 mRNA isoform. A high tumoral VEGF189 mRNA isoform expression ratio was associated with a high intratumoral microvessel count (P = .013), short survival (< 24 months; P = .001), and early postoperative relapse (< 12 months; P = .001). Survival and postoperative relapse time were significantly shorter in patients with a high compared with a low tumor VEGF189 mRNA isoform expression ratio (P = .0001 and P = .0086, respectively, log-rank test). In contrast, the VEGF165 and VEGF 206 mRNA isoform expression ratios showed no statistical correlation with tumor angiogenesis, postoperative relapse time, or survival. A high VEGF121 mRNA isoform expression ratio was associated with short survival (< 24 months) and early relapse (< 12 months). Multivariate analysis showed that VEGF 189 mRNA isoform expression, microvessel count, and nodal status were the most important independent prognostic factors for patient survival and postoperation recurrence.

CONCLUSION

The VEGF189 mRNA isoform expression ratio shows a greater correlation with tumor angiogenesis, postoperative relapse time, and survival than do the expression ratios for the VEGF121, VEGF165, and VEGF206 mRNA isoforms and can be used as a prognostic indicator for patients with non-small-cell lung cancers.

摘要

目的

本研究旨在评估四种不同血管内皮生长因子(VEGF)mRNA亚型(VEGF121、VEGF165、VEGF 189和VEGF206)的表达与非小细胞肺癌患者的临床病理特征、肿瘤血管生成及预后之间的相关性。

患者与方法

我们采用逆转录聚合酶链反应检测了57例非小细胞肺癌中四种不同VEGF mRNA亚型的表达,并采用免疫组织化学染色检测了肿瘤血管生成情况。

结果

57例肺癌样本均表达VEGF121、VEGF165和VEGF189 mRNA亚型,3例表达VEGF206 mRNA亚型。肿瘤VEGF189 mRNA亚型高表达率与肿瘤内微血管计数高(P = 0.013)、生存期短(< 24个月;P = 0.001)及术后早期复发(< 12个月;P = 0.001)相关。肿瘤VEGF189 mRNA亚型高表达率患者的生存期和术后复发时间显著短于低表达率患者(对数秩检验,P分别为0.0001和0.0086)。相比之下,VEGF165和VEGF 206 mRNA亚型表达率与肿瘤血管生成、术后复发时间或生存期无统计学相关性。VEGF121 mRNA亚型高表达率与生存期短(< 24个月)及早期复发(< 12个月)相关。多因素分析显示,VEGF 189 mRNA亚型表达、微血管计数和淋巴结状态是患者生存及术后复发最重要的独立预后因素。

结论

与VEGF121、VEGF165和VEGF206 mRNA亚型表达率相比,VEGF189 mRNA亚型表达率与肿瘤血管生成、术后复发时间及生存期的相关性更强,可作为非小细胞肺癌患者的预后指标。

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