溶酶体相关膜蛋白1在结直肠癌的表达及其与临床预后的相关性

Expression of LAMP1 and its correlation with clinical prognosis in colorectal cancer

目的 检测溶酶体相关膜蛋白1(LAMP1)在结直肠癌(CRC)的表达情况同时研究LAMP1表达与CRC重要临床病理指标,尤其是疾病预后的关系。方法 通过生物信息学分析在大数据层面检索LAMP1在CRC的表达情况和预后特性。分别在10例CRC肿瘤组织和包含60例CRC样本的组织芯片中进行qPCR和免疫组化检测,使用单因素及多因素Cox回归法及Kaplan-Meier生存曲线分析影响CRC预后的因素。结果 大数据显示LAMP1蛋白主要定位于溶酶体,在CRC细胞系上有不同程度的高表达,同时在CRC肿瘤组织中显著高于正常对照组织,高表达LAMP1的CRC患者无复发生存率和总生存率均低于低表达LAMP1患者。临床10例qPCR及免疫组化结果均显示CRC中LAMP1表达明显高于癌旁对照组织(P<0.05)。在队列60例分析中,单因素Cox模型分析示,LAMP1表达(P=0.030)、肿瘤分化(P=0.041)、CEA水平(P=0.028)及远处转移(P=0.002)与CRC病例的预后显著相关;多因素分析示,肿瘤分化(P=0.006)及远处转移(P=0.041)是其独立预后因素;生存分析示,LAMP1高表达、肿瘤分化差、CEA水平≥15 ng/mL及远处转移阳性的患者总生存期较短。结论 LAMP1在CRC中存在异常高表达且LAMP1表达与CRC恶性表型明显相关。LAMP1表达可作为CRC预后的预测指标。

Objective To detect the expression of lysosome-associated membrane protein 1(LAMP1) in colorectal cancer(CRC) and study the relationship between LAMP1 expression and important clinical and pathological indicators of CRC,especially disease prognosis.Methods The expression and prognostic characteristics of LAMP1 in CRC were retrieved through bioinformatics analysis at the big data level.qPCR and immunohistochemical(IHC) detection were performed on 10 clinical CRC tumor tissues and tissue chips containing 60 CRC samples.Univariate and multivariate Cox regression and Kaplan-Meier survival analysis were used to analyze the prognostic factors of CRC.Results Big data showed that LAMP1 protein was mainly located in lysosomes and had varying degrees of high expression in CRC cell lines,and was significantly higher in CRC tumor tissues than in normal control tissues.The recurrence free survival(RFS) and overall survival(OS) of CRC patients with high LAMP1 expression were lower than those with low LAMP1 expression.Both qPCR and IHC results of 10 clinical cases showed that the expression of LAMP1 in CRC was significantly higher than that in adjacent control tissues(P<0.05).In the analysis of 60 cases of cohort,univariate Cox model analysis showed that LAMP1 expression(P=0.030),tumor differentiation(P=0.041),CEA level(P=0.028) and distant metastasis(P=0.002) were significantly correlated with the prognosis of CRC.Multivariate analysis showed that tumor differentiation(P=0.006) and distant metastasis(P=0.041) were independent prognostic factors;Survival analysis showed that the overall survival was shorter in patients with high expression of LAMP1,poor tumor differentiation,CEA level≥15 ng/mL and positive distant metastasis.Conclusion LAMP1 is abnormal highly expressed in CRC.LAMP1 expression is significantly correlated with CRC malignant phenotype,which may serve as a predictive indicator of CRC prognosis.