Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer.
Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer.
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DOI：
10.1186/1471-2407-10-203
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发表时间：
2010-05-14
期刊：
影响因子：
3.8
通讯作者：
Lee JH
中科院分区：
文献类型：
--
作者：
Kwon KA;Kim SH;Oh SY;Lee S;Han JY;Kim KH;Goh RY;Choi HJ;Park KJ;Roh MS;Kim HJ;Kwon HC;Lee JH
血管生成是一个多步骤的过程，其中许多生长因子和细胞因子具有重要作用。血管内皮生长因子（VEGF）是一种强有力的血管生成剂，通过特异性细胞表面受体作为血管内皮细胞的特异性丝裂原。白细胞介素-6（IL-6）途径是将血管生成与恶性肿瘤联系起来的另一种机制。C-反应蛋白（CRP）是炎症的代表性标志物，已知其与许多癌症类型的疾病进展相关。本研究旨在探讨大肠癌患者术前血清VEGF、IL-6和CRP水平与疾病状态及预后的关系。143例结直肠癌根治性切除患者中有132例入选本研究。排除11例切缘阳性患者。分析VEGF、IL-6和CRP与组织学结果之间的关系时考虑的因素。研究患者预后。采用酶联免疫吸附试验（ELISA）检测血清VEGF和IL-6水平，采用免疫比浊法检测CRP水平。中位随访时间为18.53个月（范围0.73-43.17个月），患者的中位年龄为62岁（范围26-83岁）。结直肠癌患者VEGF和CRP的平均值和中位数水平显著高于正常对照组; 608 vs. 334 pg/mL和528 pg/mL，（范围122-3242）对比312（范围16-1121）（p < 0.001）; 1.05 mg/dL对比0.43 mg/dL和0.22（范围0.00-18.40）对比0.07（范围0.02-6.94）（p = 0.002）。然而，患者中IL-6的平均和中位水平并不显著高于对照组; 14.33 pg/mL vs. 5.65 pg/mL和6.00（范围1.02-139.17）vs. 5.30（4.50-13.78）（p = 0.327）。虽然IL-6和CRP水平与其他病理结果无关，但VEGF水平与肿瘤大小（p = 0.012）和CEA（p = 0.038）显著相关。当我们通过受试者工作特征（ROC）曲线确定VEGF（825 pg/mL）、IL-6（8.09 pg/mL）和CRP（0.51 mg/dL）的临界值时，我们注意到高VEGF水平倾向于降低总生存率（p = 0.053），但不显著。然而，IL-6和CRP在无病生存期（分别为p = 0.531，p = 0.701）和总生存期（分别为p = 0.563，p = 0.572）方面无显著性差异。多变量分析显示VEGF（p = 0.032）、CEA（p = 0.012）、淋巴结转移（p = 0.002）和TNM分期（p = 0.025）与总生存率独立相关。结直肠癌患者术前血清VEGF和CRP水平升高。高VEGF水平已被认为是结直肠癌患者总生存率的不良预后因素。
Angiogenesis is a multistep process in which many growth factors and cytokines have an essential role. Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells through specific cell surface receptors. The interleukin-6 (IL-6) pathway is another mechanism linking angiogenesis to malignancy. C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types. The aim of this study was to determine preoperative serum levels of VEGF, IL-6, and CRP in colorectal carcinoma, and to correlate them with disease status and prognosis. A 132 of 143 patients who underwent curative resection for colorectal cancer were enrolled in this study. 11 patients with resection margin positive were excluded. Factors considered in analysis of the relationship between VEGF, IL-6, and CRP and histological findings. Patient prognosis was investigated. Serum levels of VEGF and IL-6 were assessed using Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured using immunoturbidimetry. Median follow-up duration was 18.53 months (range 0.73-43.17 months) and median age of the patients was 62 years (range, 26-83 years). Mean and median levels of VEGF and CRP in colorectal cancer were significantly higher than in the normal control group; 608 vs. 334 pg/mL and 528 (range 122-3242) vs. 312 (range 16-1121) (p < 0.001); 1.05 mg/dL vs. 0.43 mg/dL and 0.22 (range 0.00-18.40) vs. 0.07 (range 0.02-6.94) (p = 0.002), respectively. However mean and median level of IL-6 in patients were not significantly higher than in control; 14.33 pg/mL vs. 5.65 pg/mL and 6.00 (range 1.02-139.17) vs. 5.30 (4.50-13.78) (p = 0.327). Although IL-6 and CRP levels were not correlated with other pathological findings, VEGF level was significantly correlated with tumor size (p = 0.012) and CEA (p = 0.038). When we established the cutoff value for VEGF (825 pg/mL), IL-6 (8.09 pg/mL), and CRP (0.51 mg/dL) by Receiver Operating Characteristic (ROC) curve, we noted that high VEGF levels tended to reduce overall survival (p = 0.053), but not significantly. However, IL-6 and CRP demonstrated no significance with regard to disease free survival (p = 0.531, p = 0.701, respectively) and overall survival (p = 0.563, p = 0.572, respectively). Multivariate analysis showed that VEGF (p = 0.032), CEA (p = 0.012), lymph node metastasis (p = 0.002), and TNM stage (p = 0.025) were independently associated with overall survival. Preoperative serum VEGF and CRP level increased in colorectal cancer patients. High VEGF level has been proposed as a poor prognostic factor for overall survival in patients with colorectal cancer.
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