干细胞标志物CD44及Lgr5在结直肠癌中的表达及与淋巴结和肝转移的关系

Expression of stem cell markers CD44 and Lgr5 in colorectal cancer and its relationship with lymph node and liver metastasis

目的探讨干细胞标志物CD44及Lgr5在结直肠癌中的表达及与淋巴结和肝转移的关系。方法收集天津医科大学第二医院病理科2011年1月至2016年6月间结直肠癌标本90例、癌旁组织20例、淋巴结转移灶30例、癌结节28例及结直肠癌肝转移组织30例，利用免疫组化检测CD44及Lgr5蛋白的表达情况，分析二者与患者临床病理学资料、淋巴结转移和肝转移的关系。结果结直肠癌组织中CD44和Lgr5的阳性表达率分别为68．9％和62．2％，高于癌旁组织的30．0％和15．0％（P：0．001及P〈0．001）；结直肠癌中CD44和Lgr5的表达与组织学分化、肿瘤浸润深度、是否伴有淋巴结转移和软组织癌结节及肝转移、TNM分期有关（分别为P=0．021、0．032、0．030、0．011、0．015、0．007及P=0．011、0．027、0．017、0．008、0．011、0．021）；淋巴结转移灶、癌结节及肝转移灶中CD44和Lgr5表达的阳性率（分别为93．3％、89．3％、90．0％和83．3％、89．3％、86．7％）较原发灶（68．9％和62．2％）高（P=0．007、0．032、0．022及P=0．033、0．007、0．013）；结直肠癌中CD44和Lgr5表达存在正相关关系（r=0．615，P〈0．001），两者同时阳性表达与组织学分化、是否伴有淋巴结转移和癌结节及肝转移、TNM分期有关（P=0．005、0．003、0．003、0．026、0．014）；Kaplan．Meier生存曲线显示，CD44阳性表达及CD44与Lgr5同时阳性表达结直肠癌患者的总体生存率低（P=0．030及0．001）；log-rank单因素生存分析表明组织学分化、浸润深度、淋巴结转移、伴肝转移及临床分期是患者术后生存时间的影响因素（P=0．035、0．035、0．018、0．016、0．004），Cox比例风险回归模型多因素分析显示CD44与Lgr5同时阳性表达、伴淋巴结转移、伴肝转移及临床分期是影响结直肠癌患者预后的独立因素（P=0．004、0．044、0．031、0．008）。结论CIM4和Lgr5的阳性表达与结直肠癌的恶性生物学行为有关，是促进患者局部和远处转移的重要因素，两者同时阳性表达对不良预后有提示作用。

0bjective To investigate the relationship between the expression of stem cell markers CD44 and Lgr5 and the clinicopathological features, lymph node and liver metastasis, and to analyse the value of both in evaluating the prognosis of colorectal cancer. Methods A total of 90 cases of eolorectal cancer, 20 cases of adjacent tissues, 30 cases of lymph node metastases, 28 cases of cancer nodules and 30 cases of liver metastasis of colorectal cancer were collected from Department of Pathology of the Second Hospital of Tianjin Medical University from January 2011 to June 2016. The expression of CD44 and Lgr5 protein was detected by immunohistochemistry, and the relationship between them and clinical pathological data, lymph node metastasis and liver metastasis were analyzed. Results The positive expression rates of CD44 and Lgr5 in colorectal cancer tissues were 68.9% and 62. 2% , which were significantly higher than 30. 0% and 15.0% of adjacent tissues（P = 0. 001 and P 〈 0. 001 ）. The expression of CD44 and Lgr5 in colorectal cancer was associated with histological differentiation, depth of tumor invasion, lymph node metastasis, soft tissue nodules, hepatic metastasis, and TNM staging （ P = 0. 021,0. 032,0. 030,0. 011,0. 015,0. 007 and P = 0. 011,0. 027,0. 017,0. 008,0. 011,0. 021 ）. The positive rates of CD44 and Lgr5 expression in lymph node metastases, cancer nodules and liver metastases （93.3% , 89. 3% , 90. 0% , and 83.3% , 89. 3% , 86. 7% ） were higher than those in the primary lesions（68.9% and 62. 2% ） （P =0. 007, 0. 032,0. 022 and t9 = 0. 033,0. 007,0. 013 ）. There is a positive correlation between the expression of CD44 and Lgr5 in colorectal cancer（ r = 0. 615, P 〈 0.001 ） , and both positive expression of CD44 and Lgr5 is associated with histological differentiation, lymph node metastasis and cancer nodules, liver metastasis and TNM staging（P = 0. 005,0. 003,0. 003,0. 026,0. 014）. The Kaplan-Meier survival curve showed that the survival rate of positive expression of CD44 and both positive expression of CIM4 and Lgr5 in patients with colorectal cancer was low （ P = 0. 030 and 0. 001 ） . Log-rank univariate survival analysis showed that histological differentiation, depth of invasion, lymph node metastasis, liver metastasis, and clinical stage were the influencing factors of postoperative survival time （ P = 0. 035, 0. 035,0. 018,0. 016,0. 004）. Cox proportional hazards regression model multivariate analysis showed that both positive expression of CD44 and Lgr5, lymph node metastasis, liver metastasis, and clinical stage were independent factors affecting the prognosis of patients with colorectal cancer （ P = 0. 004, 0. 044, 0. 031,0. 008 ） . Conclusions The expression of C1M4 and Lgr5 is related to the malignant biological behavior of colorectal cancer, and they are important factors in promoting local and distant metastases. Both positive expression of them have a hint of bad prognosis.