Department of Radiation Oncology, Fudan University, Shanghai, People's Republic of China.
Cancer J. 2009 Nov-Dec;15(6):519-25. doi: 10.1097/PPO.0b013e3181c6aa6b.
Lymph node metastasis (LNM) is a chief cause of morbidity and mortality in patients with hepatocellular carcinoma (HCC) after hepatectomy. The aim of this study was to investigate the relationship between the expression of CXCR4 and vascular endothelial cell growth factor (VEGF)-C and the clinicopathological features of HCC with LNM.
Immunohistochemical staining for CXCR4 and VEGF-C was performed on tissue microarrays that were constructed using tumor specimens from patients with HCC with (N = 123) or without (N = 145) LNM. The relationship between the clinicopathological features of HCC and the expression of CXCR4 and VEGF-C was analyzed using the Pearson chi(2) test, logistical regression analysis, and receiver operating characteristic analysis.
Nuclear CXCR4 expression and VEGF-C expression were positively correlated with LNM and poor outcome in HCC. Moreover, nuclear CXCR4 expression was positively correlated with VEGF-C expression (correlation coefficient 0.256). Receiver operating characteristic analysis revealed that both factors were predictive of HCC LNM {CXCR4: area under the curve, 0.695 [95% confidence interval (CI), 0.630-0.759; VEGF-C: area under the curve, 0.629 (95% CI, 0.562-0.695]}. Patients with tumors exhibiting high nuclear CXCR4 expression or high VEGF-C expression had significantly poorer overall survival than those with low tumor expression of the corresponding factors. Multivariate analysis showed that UICC T stage [odds ratio (OR), 1.615, 95% CI, 1.306-1.997], nuclear CXCR4 expression (OR, 3.998; 95% CI, 2.706-5.907), and VEGF-C expression (OR, 1.903; 95% CI, 1.203-3.011) were independent risk factors for developing HCC LNM.
These findings suggest that nuclear CXCR4 expression and VEGF-C expression can be used to identify patients with HCC at high risk for developing LNM.
淋巴结转移（LNM）是肝癌（HCC）患者肝切除术后发病率和死亡率的主要原因。本研究旨在探讨趋化因子受体 4（CXCR4）和血管内皮生长因子-C（VEGF-C）的表达与具有 LNM 的 HCC 的临床病理特征之间的关系。
采用组织微阵列免疫组化法检测 123 例伴有 LNM 的 HCC 患者和 145 例无 LNM 的 HCC 患者肿瘤标本中 CXCR4 和 VEGF-C 的表达。采用 Pearson chi(2)检验、逻辑回归分析和受试者工作特征分析（ROC 分析）分析 HCC 的临床病理特征与 CXCR4 和 VEGF-C 表达之间的关系。
核 CXCR4 表达和 VEGF-C 表达与 HCC 的 LNM 和不良预后呈正相关。此外，核 CXCR4 表达与 VEGF-C 表达呈正相关（相关系数 0.256）。ROC 分析显示，这两个因素均可预测 HCC 的 LNM [CXCR4：曲线下面积，0.695（95%置信区间，0.630-0.759；VEGF-C：曲线下面积，0.629（95%置信区间，0.562-0.695]）。核 CXCR4 表达或 VEGF-C 表达高的肿瘤患者的总生存率明显低于相应因素低表达的患者。多因素分析显示，UICC T 分期[比值比（OR），1.615，95%置信区间（CI），1.306-1.997]、核 CXCR4 表达（OR，3.998；95%CI，2.706-5.907）和 VEGF-C 表达（OR，1.903；95%CI，1.203-3.011）是 HCC 发生 LNM 的独立危险因素。
这些发现表明，核 CXCR4 表达和 VEGF-C 表达可用于识别发生 LNM 风险较高的 HCC 患者。
