Wang X F, Zhang X L, Xu L P, Shi G G, Zheng H Y, Sun B C
Department of Pathology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Zhonghua Yi Xue Za Zhi. 2018 Sep 25;98(36):2899-2904. doi: 10.3760/cma.j.issn.0376-2491.2018.36.005.
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. A total of 90 cases of colorectal 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. 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(=0.001 and <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(=0.021, 0.032, 0.030, 0.011, 0.015, 0.007 and =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%)(=0.007, 0.032, 0.022 and =0.033, 0.007, 0.013). There is a positive correlation between the expression of CD44 and Lgr5 in colorectal cancer(r=0.615, <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(=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 CD44 and Lgr5 in patients with colorectal cancer was low(=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(=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(=0.004, 0.044, 0.031, 0.008). The expression of CD44 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.
探讨干细胞标志物CD44和Lgr5的表达与临床病理特征、淋巴结及肝转移之间的关系,并分析二者在评估结直肠癌预后中的价值。收集2011年1月至2016年6月天津医科大学第二医院病理科90例结直肠癌、20例癌旁组织、30例淋巴结转移灶、28例癌结节及30例结直肠癌肝转移灶。采用免疫组织化学法检测CD44和Lgr5蛋白的表达,并分析其与临床病理资料、淋巴结转移及肝转移的关系。结直肠癌组织中CD44和Lgr5的阳性表达率分别为68.9%和62.2%,显著高于癌旁组织的30.0%和15.0%(P = 0.001和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、淋巴结转移、软组织结节、肝转移及TNM分期相关(P = 0.021、0.032、0.030、0.011、0.015、0.007和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(93.3%、89.3%、90.0%和83.3%、89.3%、86.7%)高于原发灶(68.9%和62.2%)(P = 0.007、0.032、0.022和P = 0.033、0.007、0.013)。结直肠癌中CD44与Lgr5的表达呈正相关(r = 0.615,P<0.001),CD44和Lgr5均阳性表达与组织学分化、淋巴结转移、癌结节、肝转移及TNM分期相关(P = 0.005、0.003、0.003、0.026、0.014)。Kaplan-Meier生存曲线显示,结直肠癌患者中CD44阳性表达及CD44和Lgr5均阳性表达者的生存率较低(P = 0.030和P = 0.001)。Log-rank单因素生存分析显示,组织学分化、浸润深度、淋巴结转移、肝转移及临床分期是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和Lgr5均阳性表达、淋巴结转移、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)。CD44和Lgr5的表达与结直肠癌的恶性生物学行为有关,是促进局部和远处转移的重要因素。二者均阳性表达提示预后不良。