核不均一核糖核蛋白A1和白细胞分化抗原44在结直肠癌中表达及临床意义

Expression of nuclear heterogeneous ribonucleoprotein A1 and cluster of differentiation 44 proteins in colorectal cancer and its clinical significance

目的探讨核不均一核糖核蛋白A1(hnRNPA1)和白细胞分化抗原44(CD44)在结直肠癌(CRC)组织中的表达及临床意义。方法利用基因表达谱数据动态分析(GEPIA)数据库检索hnRNPA1和CD44 mRNA在CRC组织中的表达, 收集2015年1月至2017年1月咸宁市中心医院联合遵义医科大学附属医院经病理确诊的155例CRC癌组织及50例癌旁组织, 采用免疫组织化学方法检测当中组织hnRNPA1和CD44蛋白表达, χ^(2)检验分析两者与患者临床病理特征、生存情况的关系。结果 GEPIA数据库分析结果表明hnRNPA1与CD44 mRNA在CRC癌组织中高表达。免疫组织化学结果显示hnRNPA1、CD44蛋白在CRC癌组织中的表达明显高于其癌旁组织(hnRNPA1:χ^(2)=31.230, P<0.01;CD44:χ^(2)=21.150, P<0.01)。hnRNPA1蛋白的表达与肿瘤大小、分化程度、浸润深度、淋巴结转移、TNM分期及癌胚抗原(CEA)相关(χ^(2)=9.913、7.958、11.932、22.627、25.981、22.670, P<0.05);与患者性别及年龄无关(χ^(2)=0.284、0.164, P>0.05)。CD44蛋白的表达与分化程度、浸润深度、淋巴结转移、TNM分期及CEA相关(χ^(2)=4.645、4.626、6.095、6.371、13.821, P<0.05), 与性别、年龄、肿瘤大小无关(χ^(2)=0.251、0.103、2.524, P>0.05)。Spearman相关分析提示hnRNPA1与CD44在CRC中的表达呈正相关(r=0.272, P<0.01)。Kaplan-Meier生存分析发现hnRNPA1、CD44高表达组5年总生存率均低于其低表达组(hnRNPA1:χ^(2)=23.92, P<0.01;CD44:χ^(2)=15.15, P<0.01)。Cox分析hnRNPA1[风险比(HR)=2.714, 95%可信区间(CI)=1.305~5.646, P< 0.01]、CEA(HR=2.538, 95%CI=1.599~4.030, P<0.01)及TNM分期(HR=3.978, 95%CI=1.253~12.629, P<0.05)作为影响结直肠癌手术后总生存率的独立预后因子。结论 hnRNPA1可能协同CD44参与CRC发生发展过程, 并作为CRC潜在预后标志物。

Objective To investigate the expression and clinical significance of heterogeneous ribonucleoprotein A1(hnRNPA1)and cluster of differentiation 44(CD44)in colorectal cancer(CRC)tissues.Methods The expression levels of hnRNPA1 and CD44 mRNA in CRC tissues were analyzed by the Gene Expression Profiling Interactive Analysis(GEPIA)database.The expression levels of hnRNPA1 and CD44 in 155 cases of CRC tissues and 50 cases of adjacent tissues pathologically confirmed from January 2015 to January 2017 on Xianning Central Hospital and the Affiliated Hospital of Zunyi Medical University were detected by immunohistochemistry.The relationship between the expression of hnRNPA1 and CD44 proteins and the clinicopathological characteristic,the patient survival was analyzed by χ^(2) test.Results GEPIA database analysis showed that the expression of hnRNPA1 and CD44 mRNA in CRC tissues was elevated.The results of immunohistochemistry demonstrated that the expression of hnRNPA1 and CD44 proteins in CRC tissues was significantly higher than that in adjacent normal tissues(hnRNPA1:χ^(2)=31.230,P<0.01;CD44:χ^(2)=21.150,P<0.01).The expression of hnRNPA1 protein was associated with tumor size,degree of differentiation,depth of tumor invasion,lymph node metastasis,TNM stage and carcinoembryonic antigen(CEA)(χ^(2)=9.913,7.958,11.932,22.627,25.981,22.670,P<0.05),but not with gender and age(χ2=0.284,0.164,P>0.05).The expression of CD44 protein was associated with degree of differentiation,depth of tumor invasion,lymph node metastasis,TNM stage and CEA(χ^(2)=4.645,4.626,6.095,6.371,13.821,P<0.05),but not with gender,age and tumor size(χ^(2)=0.251,0.103,2.524,P>0.05).Spearman correlation analysis indicated that hnRNPA1 was positively correlated with the expression of CD44 in CRC tissues(r=0.272,P<0.01).Kaplan-Meier survival analysis showed that the 5-year overall survival rate in hnRNPA1 and CD44 high expression group was significantly lower than that in low expression group(hnRNPA1:χ^(2)=23.92,P<0.01;CD44:χ^(2)=15.15,P<0.01).The Cox analysis showed that hnRNPA1[hazard ratio(HR)=2.714,95%confidence interval(CI)=1.305-5.646,P<0.01],CEA(HR=2.538,95%CI=1.599-4.030,P<0.01)and TNM stage(HR=3.978,95%CI=1.253-12.629,P<0.05)were the independent prognostic factors affecting overall survival after CRC surgery.Conclusion HnRNPA1 may be associated with CD44 to participate in the occurrence and development of CRC and serve as a potential prognostic marker for CRC.