结直肠癌原发灶中CXCR6的表达与临床意义

Expression and clinical significance of chemokine receptor CXCR6 in primary colorectal cancer

目的:明确趋化因子受体CXCR6在结直肠癌原发灶中的表达特点及临床意义。方法:收集2004年8月至2008年12月中山大学附属第一医院手术切除的143例结直肠癌标本及29例癌旁组织,应用免疫组化方法检测CXCR6的表达,采用Image-Pro Plus 6.0软件分析图片的平均累积吸光度(mIA),分析CXCR6与同时性肝转移及预后的关系。结果:CXCR6在结直肠癌组织中呈不同程度的阳性表达,在癌旁正常组织中弱表达或不表达。结直肠癌原发灶中CXCR6的mIA在0.41～2.84之间,平均为1.54±0.04,其中同时性肝转移病例为1.63±0.05,无肝转移病例为1.41±0.08,两组比较差异有统计学意义(P<0.05)。以mIA值1.54为界,将病例划分为CXCR6低表达组(mIA<1.54)和CXCR6高表达组(mIA≥1.54)。CXCR6高表达患者的总生存率显著较低表达组差,两组差异有统计学意义(P<0.05)。多因素Cox回归分析发现年龄(P<0.05)、淋巴结转移(P<0.05)和同时性肝转移(P<0.01)为结直肠癌患者预后的独立危险因素,CXCR6为非独立危险因素。CXCR6表达与IV期肝转移患者预后无关(P>0.05),与I～III期结直肠癌患者预后呈负相关(P<0.01)。结论:CXCR6与结直肠癌肝转移的发生相关,它有望成为结直肠癌肝转移治疗的一个重要靶点。

AIM ： To investigate the expression of chemokine receptor CXCR6 in primary colorectal cancer and determine the association between CXCR6 expression and synchronous liver metastasis/prognosis. METHODS ： The color- ectal cancer tissues from 143 patients were collected from August 2004 to December 2008 in the First Affiliated Hospital, Sun Yat - sen University. Twenty - night cases of the adjacent normal colorectal tissues were enrolled as controls. The ex- pression of CXCR6 was detected by immunohistochemistry and the mean intergrated absorbance （mlA） was calculated by Image - Pro Plus 6.0 software. The relationship between CXCR6 expression and synchronous liver metastasis/prognosis was analyzed. RESULTS ： The CXCR6 staining was mainly positive in colorectal cancer tissues but not in adjacent normal colo- rectal tissues. The mlA of.CXCR6 in colorectal cancer was 1.54 ±0.04 （range： 0.41 -2.84）, and was 1.63 ±0.05 and 1.41 ±0.08 （P〈0.05） in the cases with （n =83） or without （n =60） synchronous liver metastasis, respectively. According to the mean m/A of CXCR6 （ 1.54）, the cases was divided into high CXCR6 group （ mlA ≥ 1.54） and low CXCR6 group （mlA 〈 1.54）. The overall survival rate in high CXCR6 group was significantly lower than that in low CXCR6 group （ P 〈 0.05）. In multivariate Cox regression models, age （ P 〈 0.05 ）, lymph node metastasis （ P 〈 0.05 ） and synchronous liver metastasis （P 〈0. 01 ） but not CXCR6 were identified as independent risk factors for poor outcome. In subgroup analysis, high CXCR6 expression was associated with poorer survival in the patients with stage I - III colorectal cancer （P 〈 0. 01 ） but not those with synchronous liver metastasis （P 〉 0.05 ）. CONCLUSION： CXCR6 in primary colorectal cancer tissues is associated with liver metastasis. It may become a potential target for the treatment of colorectal cancer liver metastasis.