结肠癌galectin-3蛋白的表达与微环境Foxp3⁺、IL-17⁺淋巴细胞的相关性

Correlation between Galectin-3 Protein and Foxp3⁺, IL-17⁺ Lymphocytes in Colon Cancer Microenvironment

摘要: 背景：Galectin-3(gal-3)参与多种肿瘤的发生、发展，并可调控免疫细胞的活性。肿瘤微环境中Th17细胞和调节性T细胞(Treg)可影响肿瘤的发展和归转。目前关于结肠癌gal-3蛋白与微环境免疫细胞的关系研究尚少，因此本研究拟分析肿瘤gal-3的表达与微环境Foxp3⁺、IL-17A⁺淋巴细胞的相关性，为深入了解结肠癌相关蛋白对免疫微环境的作用提供基础。方法：收集2011-2012年在广州医科大学附属肿瘤医院进行手术切除的结肠癌组织50例和10例对照正常组织，通过免疫组化技术检测组织中gal-3、IL-17A、Foxp3的表达情况，结合临床病理参数分析三者间的表达意义和相关性。结果：Gal-3蛋白主要表达于肿瘤细胞的胞浆，Foxp3蛋白主要表达在间质组织淋巴细胞的胞核中，IL-17A见于间质淋巴细胞的胞浆。结果显示肿瘤组织和间质中的gal-3、Foxp3和IL-17A阳性表达率均显著高于正常结肠上皮组织。其中gal-3在中晚期结肠癌中表达水平明显高于早期病例，而Foxp3⁺、IL-17A⁺淋巴细胞比例在中晚期病例中也显著升高。相关性分析显示，肿瘤组织的gal-3表达水平与肿瘤间质中Foxp3⁺细胞和IL-17A⁺细胞的阳性比例呈正相关(r = 0.608，P < 0.001；r = 0.289，P = 0.042)，即肿瘤细胞表达gal-3越高，间质组织中浸润的Fopx3⁺细胞和IL-17A⁺细胞越多。结论：Gal-3蛋白可能促进微环境中Foxp3⁺、IL-17A⁺淋巴细胞的浸润参与结肠癌的生长和进展。

Abstract: Background: Galectin-3 (gal-3) involves in tumor development, progression, and regulates im-mune cells activity. Th17 cells and T regulatory cells (Treg) in tumor environment could affect tumor progression and prognosis. Recently few researches investigated the relation between gal-3 and immune cells in colon cancer microenvironment, therefore this research aimed to demonstrate the correlation between gal-3 and Foxp3⁺, IL-17A⁺ lymphocytes in colon cancer microenvironment, for further investigating the effect on immune microenvironment from colon cancer- associated protein. Methods: From 2011 to 2012, fifty colon cancer tissue samples and 10 adjacent normal tissues after resection in Affiliated Cancer Hospital of Guangzhou Medical University were collected. Expressions of gal-3, IL-17A and Foxp3 were detected by using immuno histochemistry (IHC) technique. Correlation and significance among these three markers were analyzed with clinical-pathological data. Results: Gal-3 was mainly expressed in cytoplasm of tumor cells, Foxp3 was often found in cellular nuclear of stroma lymphocytes, and IL-17A was expressed in cytoplasm of stroma lymphocytes. Analysis showed the positive expressions of gal-3, Foxp3 and IL-17A were all significantly higher than in normal colon tissues. Expressions of gal-3 in late stage cases were much higher than in early cases, as well as the Foxp3⁺ lymphocytes and IL-17A⁺ lymphocytes. Univariate analysis revealed stroma infiltrating Foxp3⁺ lymphocytes and IL-17A⁺ lymphocytes had positive correlation with tumoral gal-3 expression (r = 0.608, P < 0.001, r = 0.289, P = 0.042), which means the higher expression of gal-3 in tumor was, the more stroma infiltrating Foxp3⁺ lymphocytes and IL-17A⁺ lymphocytes were. Conclusion: Gal-3 might promote Foxp3⁺ lymphocytes and IL-17A⁺ lymphocytes infiltration in tumor microenvironment and involve in colon cancer growth and development.