Lv Xiao-Hong, Liu Bao-Quan, Li Xue-Mei, Wang Xiang-Chen, Li Xin-Lei, Ahmed Naila, Zhang Ya-Fang
Department of Anatomy, Harbin Medical University, Harbin, People's Republic of China.
Anat Rec (Hoboken). 2016 Jun;299(6):741-7. doi: 10.1002/ar.23338. Epub 2016 Apr 4.
Vascular endothelial growth factor-C (VEGF-C) is a key regulator in lymphangiogenesis, and is overexpressed in various malignancies. Integrin α4β1, a new member of the VEGF-C/VEGF receptor pathway, was found to be overexpressed in melanoma tumors. However, little is known regarding the potential role of integrin α4β1 in lymphangiogenesis and other solid tumors. The aim of this study was to investigate the expression patterns of integrin α4 and VEGF-C in relation to lymphangiogenesis and clinicopathological parameters in human colon cancer. The expression of integrin α4, VEGF-C, and VEGFR-3 was assessed in 71 human colon cancer tissues and 30 paracancerous normal tissues by immunohistochemical staining. Lymphatic microvessel density (LMVD) was measured after D2-40-labeling, and the correlations among different factors were statistically analyzed. The expression of integrin α4, VEGF-C, VEGFR-3, and LMVD was higher in colon cancer tissues compared with the normal paracancerous colon tissues. There was a positive correlation between the expression of integrin α4 and VEGF-C. Integrin α4 and VEGF-C were significantly associated with the clinicopathological parameters (LMVD, Duke's stage, and lymph node metastasis). Kaplan-Meier analyses indicated that patients with high integrin α4 or VEGF-C expression had significantly shorter overall survival and tumor-free survival time. Multivariate analyses suggested that integrin α4 and VEGF-C may serve as independent prognostic factors for human colon cancer. Both integrin α4 and VEGF-C are involved in lymphangiogenesis and lymphatic metastasis. Our results demonstrated that integrin α4 is a novel prognostic indicator for human colon cancer. Anat Rec, 299:741-747, 2016. © 2016 Wiley Periodicals, Inc.
血管内皮生长因子C（VEGF-C）是淋巴管生成的关键调节因子，在多种恶性肿瘤中过表达。整合素α4β1是VEGF-C/VEGF受体途径的新成员，在黑色素瘤肿瘤中被发现过表达。然而，关于整合素α4β1在淋巴管生成及其他实体瘤中的潜在作用知之甚少。本研究的目的是探讨整合素α4和VEGF-C在人结肠癌中与淋巴管生成及临床病理参数相关的表达模式。通过免疫组织化学染色评估了71例人结肠癌组织和30例癌旁正常组织中整合素α4、VEGF-C和VEGFR-3的表达。在进行D2-40标记后测量淋巴管微血管密度（LMVD），并对不同因素之间的相关性进行统计学分析。与正常癌旁结肠组织相比，结肠癌组织中整合素α4、VEGF-C、VEGFR-3的表达及LMVD更高。整合素α4与VEGF-C的表达之间存在正相关。整合素α4和VEGF-C与临床病理参数（LMVD、杜克分期和淋巴结转移）显著相关。Kaplan-Meier分析表明，整合素α4或VEGF-C高表达的患者总生存期和无瘤生存期明显较短。多因素分析提示，整合素α4和VEGF-C可能是人结肠癌的独立预后因素。整合素α4和VEGF-C均参与淋巴管生成和淋巴转移。我们的结果表明，整合素α4是人类结肠癌的一种新的预后指标。《解剖学记录》，299:741-747，2016年。©2016威利期刊公司。
