CD44与CD133蛋白在胃癌组织中的表达及其临床意义

Expressions of CD133 and CD44 Protein in Primary Lesion of Gastric Cancer and Its Clinical Significance

目的研究肿瘤干细胞标志物CD44及CD133蛋白的表达与胃癌临床病理特征和预后的关系。方法应用免疫组化方法检测100例胃癌组织中CD44和CD133蛋白的表达情况,并对CD133及CD44表达与胃癌患者的临床病理资料和生存率进行统计分析。结果 CD133和CD44蛋白均主要表达在细胞膜,少量在细胞浆中表达。两者的表达均与患者的年龄和性别无关(P>0.05),但与肿瘤的大小、组织学分化程度、血管浸润、淋巴管浸润、淋巴结转移以及pTMN分期有关,肿瘤直径越大(CD44 P=0.015;CD133 P=0.002)、组织学分化程度越差(CD44P=0.008;CD133 P=0.019)、有血管浸润(CD44 P=0.043;CD133 P=0.023)、有淋巴管浸润(CD44 P=0.020;CD133P=0.044)、有淋巴结转移(CD44 P=0.002;CD133 P=0.004)、肿瘤浸润越深(CD44 P=0.006;CD133 P=0.021)以及pTNM分期越高(CD44 P=0.034;CD133 P=0.001),其CD44和CD133蛋白的表达阳性率越高。CD44+CD133+双阳性表达与患者的年龄、性别、肿瘤的组织学分化程度以及血管浸润均无关(P>0.05),但与肿瘤大小、淋巴管浸润、肿瘤T分期、N分期以及pTNM分期有关,其中,肿瘤直径越大(P=0.010)、有淋巴管浸润(P=0.003)、有淋巴结转移(P=0.045)、肿瘤浸润越深(P=0.041)以及pTNM分期越高(P=0.049),其CD44+CD133+双阳性表达率越高。单因素生存分析结果显示,淋巴结转移(P<0.001)、TNM分期(P=0.013)、CD44蛋白阳性表达(P=0.005)、CD133蛋白阳性表达(P=0.002)以及CD44+CD133+双阳性表达(P<0.001)和患者的3年生存率均有关。Spearman等级相关分析结果表明,CD44蛋白的表达与CD133蛋白的表达呈正相关(r=0.207,P=0.039)。logistic回归分析提示CD44+CD133+蛋白双阳性表达是淋巴结转移(P=0.038)的独立危险因素。Cox风险回归多因素生存分析显示,淋巴结转移(P=0.006)以及CD44和CD133蛋白的共表达(P=0.003)是影响胃癌患者术后生存的独立预后因素。结论 CD44和CD133可作为胃癌干细胞的肿瘤标志物;CD44与CD133蛋白的共表达是影响胃癌患者预后的独立危险因素,与患者预后密切相关,其表达水平越高,预后越差。

Objective To investigate the expressions of CD133 and CD44 protein in primary lesions of gastric cancer and its clinical significance. Methods The expressions of CD44 and CD133 protein in gastric cancer tissues of 100 patients with gastric cancer were detected by immunohistocheimcal stainings. The relation between the expressions of CD44 and CD133 protein and the clinicopathologic characters were analyzed. Results Both CD44 and CD133 protein were expressed on the cell membranes. No correlation were found between CD44/CD133 and the clinicopathologicparameters include gender and age （P〉0. 05）, but the positive expression rate of CD44/CD133 with diameter 〉5 cm was significantly higher than that tumor with diameter ~〈 5 cm （CD44 P=0. 150; CD133 P=0. 056）, and correlated with the tissue differentiation （CD44 P=0. 008; CD133 P=0. 007）, vascular invasion （CD44 P=0. 043; CD133 P=0. 023）, lymphatic vessel invasion （CD44 P=0. 020; CD133 P=0. 044）, lymph nodes metastasis （CD44 P=0. 002; CD133 P=0. 004）, inva- sion depth of tumor （CD44 P=0. 006; CD133 P=0. 021）, and pTNM stage （CD44 P=0. 034; CD133 P=0. 001）. No correlation were found between the co-expression of CD44 and CD 133 protein and the clinicopathologic parameters include gender, age, tissue differentiation, and vascular invasion （P〉 0. 05）, but the positive co-expression rate of CD44 and CD133 with diameter 〉 5 cm was significantly higher than that tumor with diameter ≤ 5 cm （P=0. 010）, and correlated with lymphatic vessel invasion （P=0. 003）, lymph nodes metastasis （P=0. 045）, invasion depth of tumor （P=0. 041）, and pTNM stage （P=0. 049）. The Spearman rank correlation analysis showed that there was positive correlation between the expressions of CD44 and CD133 protein （r=0. 207, P=0. 039）. Univariate analysis showed that lymph nodes metastasis （P〈 0. 001）, pTNM stages （P=0. 013）, CD44 protein expression （P=0. 005）, CD133 protein expression （P=0. 002）, and co-expression of CD44 and CD 133 protein （P〈 0. 001） were significantly correlated with 3-year survival rate of pati- ents with gastric cancer respectively. Logistic regression analysis revealed that lymph node metastasis （P=0. 038） was independent risk factor for co-expression of CD44 and CD133 protein. Multivariate analysis with the Cox regression models showed that co-expression of CD44 and CD133 protein （P=0. 003） and lymph node metastasis （P=0. 006） were significantly associated with poor prognosis. Conclusions CD44 and CD 133 protein may be considered as robust cancer stem cell markers in gastric cancer. The co-expression of CD44 and CD133 protein is the independent prognosis factor for gastric cancer and strongly associated with poor prognosis when they are expressed more high.