Ishigami S I, Arii S, Furutani M, Niwano M, Harada T, Mizumoto M, Mori A, Onodera H, Imamura M
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Br J Cancer. 1998 Nov;78(10):1379-84. doi: 10.1038/bjc.1998.688.
Vascular endothelial growth factor (VEGF) may affect the phenotype of cancer cells, such as growth velocity and metastatic potential, due to its probable multifunctional property including a mitogenic activity for vascular endothelial cells. The present study was designed to investigate the association of VEGF mRNA expression with progression and metastasis of human colorectal cancer. The level of VEGF mRNA expression was quantified by Northern blot hybridization in tumorous and non-tumorous tissues obtained from 60 primary colorectal cancer patients. The ratio of the former to the latter was defined as the VEGF T/N ratio, and the prognostic significance of this ratio, following surgery, in addition to the relationship to progression and metastatic potential, was evaluated. The value of the VEGF T/N ratio was significantly correlated with the depth of tumour infiltration (P=0.046), the incidence of liver metastasis (P < 0.0001) and lymph node metastasis (P=0.036). Patient prognosis was estimated by the Kaplan-Meier method and the log-rank test. When the VEGF T/N ratio was higher than 4.8 for which the chi2 value of the log-rank test was maximal, the tumour was defined as showing overexpression of VEGF mRNA. Patients with overexpression of VEGF mRNA demonstrated poorer survival than patients without overexpression of VEGF mRNA (P < 0.001). The overall estimated hazard ratio for death in patients with overexpression of VEGF mRNA was 1.94 according to a multivariate analysis (P=0.005). Thus, VEGF is associated with the progression, invasion and metastasis of colorectal cancer, and overexpression of VEGF mRNA in the primary tumour is assumed to be closely correlated with poor prognosis in colorectal cancer patients. Moreover, the VEGF T/N ratio may be used as an independent prognostic marker in colorectal cancer patients.
血管内皮生长因子（VEGF）可能因其具有包括对血管内皮细胞的促有丝分裂活性在内的多种功能特性，而影响癌细胞的表型，如生长速度和转移潜能。本研究旨在探讨VEGF mRNA表达与人类结直肠癌进展和转移的相关性。通过Northern印迹杂交对60例原发性结直肠癌患者的肿瘤组织和非肿瘤组织中VEGF mRNA表达水平进行定量。将前者与后者的比值定义为VEGF T/N比值，并评估该比值在手术后的预后意义，以及与进展和转移潜能的关系。VEGF T/N比值与肿瘤浸润深度（P = 0.046）、肝转移发生率（P < 0.0001）和淋巴结转移（P = 0.036）显著相关。采用Kaplan-Meier法和对数秩检验评估患者预后。当VEGF T/N比值高于4.8（此时对数秩检验的chi2值最大）时，肿瘤被定义为VEGF mRNA过表达。VEGF mRNA过表达的患者生存率低于未过表达的患者（P < 0.001）。多因素分析显示，VEGF mRNA过表达患者的总体死亡风险比为1.94（P = 0.005）。因此，VEGF与结直肠癌的进展、侵袭和转移相关，原发性肿瘤中VEGF mRNA过表达被认为与结直肠癌患者的不良预后密切相关。此外，VEGF T/N比值可作为结直肠癌患者独立的预后标志物。
