Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, China.
BMC Cancer. 2009 Dec 10;9:432. doi: 10.1186/1471-2407-9-432.
Hypoxia-inducible factor 1 alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are frequently overexpressed in numerous types of cancers and are known to be important regulators of angiogenesis. Until now, few studies have been carried out to investigate the prognostic role of these factors in solid tumors, especially in colorectal cancer (CRC). The purpose of this study was to evaluate the expression of HIF-1alpha and VEGF in CRC tissues, and to analyze the association of these two factors with several clinical and pathological characteristics, and patients' survival.
Paraffin-embedded tissue samples were retrospectively collected from 71 CRC patients, who received surgical resection between 2001 and 2002, with a median follow-up of 5 years. We examined the patterns of expression of HIF-1alpha and VEGF by immunohistochemistry method. Statistical analysis was performed with univariate tests and multivariate Cox proportional hazards model to evaluate the differences.
Expression of HIF-1alpha and VEGF was positively observed in 54.93% and 56.34% among the patients, respectively. HIF-1alpha and VEGF status were significantly associated with tumor stage, lymph nodes and liver metastases (P < 0.05). Expression of both HIF-1alpha and VEGF remained significantly associated with overall survival (OS) (P < 0.01), and HIF-1alpha was positively correlative to VEGF in CRC (r = 0.72, P < 0.001).
HIF-1alpha and VEGF could be used as biomarkers indicating tumors in advanced stage and independently implied poor prognosis in patients with CRC. Treatment that inhibits HIF-1alpha might be a promising targeted approach in CRC to exhibit its potential to improve outcomes in future perspective, just as VEGF targeting has proved to be.
缺氧诱导因子 1 阿尔法（HIF-1α）和血管内皮生长因子（VEGF）在许多类型的癌症中经常过度表达，并且已知是血管生成的重要调节剂。到目前为止，很少有研究调查这些因素在实体瘤中的预后作用，特别是在结直肠癌（CRC）中。本研究旨在评估 HIF-1α和 VEGF 在 CRC 组织中的表达，并分析这两种因子与几种临床和病理特征以及患者生存的关系。
回顾性收集了 71 例 CRC 患者的石蜡包埋组织样本，这些患者于 2001 年至 2002 年接受了手术切除，中位随访时间为 5 年。我们通过免疫组织化学方法检查了 HIF-1α和 VEGF 的表达模式。采用单因素检验和多因素 Cox 比例风险模型进行统计分析，以评估差异。
在 54.93%的患者中观察到 HIF-1α和 VEGF 的表达呈阳性，分别为 56.34%。HIF-1α和 VEGF 状态与肿瘤分期、淋巴结和肝转移显著相关（P <0.05）。HIF-1α和 VEGF 的表达均与总生存（OS）显著相关（P <0.01），并且 HIF-1α在 CRC 中与 VEGF 呈正相关（r = 0.72，P <0.001）。
HIF-1α和 VEGF 可作为标志物，提示肿瘤处于晚期，并独立预示 CRC 患者预后不良。抑制 HIF-1α的治疗可能是 CRC 的一种有前途的靶向治疗方法，从未来的角度来看，它有可能改善疗效，正如 VEGF 靶向治疗已经证明的那样。
