趋化因子受体CXCR4在结直肠癌组织中的表达及其与临床病理特征的关系

目的 观察趋化因子受体CXCR4在结直肠癌组织中的表达及其临床意义,探讨基质衍生因子SDF-1(CXCL12)-CXCR4生物学轴在结直肠癌侵袭转移中的作用.方法 免疫组织化学法检测53例结直肠癌组织及27例正常黏膜组织中CXCR4的表达及分布,并分析高表达CXCR4与结直肠癌患者临床病理特征的关系.反转录.聚合酶链反应(RT-PCR)、Western印迹方法检测27例结直肠癌肿瘤组织、正常黏膜及5例肝转移灶内CXCR4 mRNA表达及CXCR4蛋白表达水平.结果 53例结直肠癌组织中CXCR4表达阳性率为73.6%,高表达率(表达超过50%细胞)为45.3%;有淋巴结转移组CXCR4高表达率(65.4%)明显高于无淋巴结转移组(25.9%)(P＜0.01),并与肿瘤血管淋巴管浸润有关.随着临床分期的增加,肿瘤组织中CXCR4高表达率有升高趋势.但差异无统计学意义(P＞0.05).CXCR4的表达与患者肿瘤部位、大小、浸润深度无关(P＞0.05).27例新鲜结直肠癌组织中CXCR4 mRNA及蛋白表达水平明显高于相应的正常黏膜组织(P＜0.01);5例肝转移灶组织中CXCR4表达显著高于对应的原发灶(P＜0.01).结论 趋化因子受体CXCR4是一类参与结直肠癌病程进展的重要分子.CXCL12-CXCR4信号通路有望成为结直肠癌治疗的新靶点.

Expression of chemokine receptor CXCR4 in colorectal carcinoma and its relationship with clinicopathologicai parameters

Objective To investigate the expression of chemokine receptor CXCR4 in colorectal carcinoma and its relationship with the clinicopathological parameters,and to reveal the role of CXCL12/CXCR4 in the invasion and metastasis of colorectal carcinoma. Methods CXCR4 expression was studied in 53 colorectal cancer tissues and 27 normal tissues by immunohistocbemistry. Its relationship with clinieopathological characteristics of colorectal cancer patients were analyzed. The CXCR4 expression in tumor and normal specimens and its metastatic sites were assessed by RT-PCR and Western blot.Results Fifty-three colorectal cancer patients,collected from July 2005 to February 2007 in our hospital ,were enrolled in this study. CXCR4 was positive in 39 cancer tissue specimens (73.6%) and its high expression rate (in ＞ 50% of cells) was 45.3%.High CXCR4 expression rate was significantly higher in patients with lymph node metastases (N1+N2: 65.4%) than that in those without metastases(No 25.9%).There were also associations between the high CXCR4 expression and the vascular and lymphatic vessel invasions (P＜0.01). Meanwhile, there was a rising trend of high expression rate according to American Joint Committee on Cancer (AJCC) stage and pathologic grade,but no significant difference was found (P＞0.05). There were no significant correlation of CXCR4 expression with clinicopathological parameters such as tumor location, tumor size, depth of tumor invasion (P＞0.05).In addition,the CXCR4 mRNA expression in primary tumor specimens (n=27)from AJCC stage Ⅳ patients was significantly higher than that in normal tissues. CXCR4 mRNA expression of liver metastasis specimens (n=5) was significantly higher as compared with the primary colorectsl cancer specimens (P＜0.01). Conclusions Chemokine receptor CXCR4 is associated with the progression ofcolorectal carcinoma.High CXCR4 expression is associated with metastasis.The CXCL12-CXCR4 signaling pathway may be a potential novel target of therapy for patients with colorectal cancer.