艾杜糖醛酸-2-硫酸酯酶与结直肠癌转移及预后的关系  

Relationships of iduronic acid-2-sulfatase with metastasis and prognosis of colorectal cancer

作　　者：杨泽宇 何小丽 唐焘 王迪 廖雪梅 余时沧 YANG Zeyu;HE Xiaoli;TANG Tao;WANG Di;LIAO Xuemei;YU Shicang(Institute of Pathology, Southwest Cancer Center,First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China;Department of Stem Cell and Regenerative Medicine, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China)

机构地区：[1]陆军军医大学(第三军医大学)第一附属医院全军临床病理学研究所,西南癌症中心,重庆400038 [2]陆军军医大学(第三军医大学)第一附属医院干细胞与再生医学科,重庆400038

出　　处：《第三军医大学学报》2019年第17期1635-1641,共7页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81572880)~~

摘　　要：目的寻找与结直肠癌转移相关并具有预后预测意义的溶酶体分子。方法获取TCGA数据库结直肠癌数据集(Colon Adenocarcinoma TCGA-632)结直肠癌临床样本信息和基因转录组测序表达矩阵;通过基于LASSO(least absolute shrinkage and selection operator)算法的Logistic回归筛选与远处转移相关的溶酶体基因;进一步利用基于LASSO算法的COX回归模型,筛选与结直肠癌患者预后相关的基因,并选择回归系数最大的艾杜糖醛酸-2-硫酸酯酶(iduronic acid-2-sulfatase,IDS)进行研究;收集本院2007-2008年50例结直肠癌患者肿瘤组织标本进行免疫组织化学染色,分析组织中IDS表达量与转移及预后的关系。结果 TCGA数据库分析显示:发生淋巴结转移的结直肠癌患者IDS mRNA相对表达量高于无淋巴结转移的患者(N0vsN1-2:-0.103±0.073 vs 0.303±0.123,P=0.003);发生远处转移的结直肠癌患者IDS mRNA相对表达量高于无远处转移的患者(M0vsM1:0.017±0.071 vs 0.636±0.296,P=0.003);IDS高表达患者的预后较低表达患者不良(总体生存期:P=0.008;无病生存期:P=0.007);COX回归分析显示:IDS mRNA高表达是结直肠癌患者预后不良的独立预测因素(P=0.014,风险系数为2.651,95%CI:1.217~5.775);50例结直肠癌组织免疫组化分析显示:发生淋巴结转移的结直肠癌患者IDS mRNA相对表达量高于无淋巴结转移的患者(N0vs N1-3:27.324±0.698 vs 40.674±3.528,P=3.0×10^-5);发生远处转移的结直肠癌患者IDS mRNA相对表达量高于无远处转移的患者(M0vs M1:27.941±0.952 vs 39.320±3.467,P=1.2×10^-5);IDS高表达患者预后不良(P=7.2×10^-5);COX回归分析显示:IDS高表达是预后不良的独立预测因素(P=0.008,风险系数为5.847,95%CI:1.585~21.568)。结论 IDS高表达的结直肠癌患者转移发生率高、预后差,IDS可作为结直肠癌患者独立预后预测因子。Objective To select lysosomal molecules related to metastasis and prognosis of colorectal cancer. Methods The clinical sample information and gene transcriptome sequencing expression matrix of colorectal cancer TCGA database(Colon Adenocarcinoma TCGA-632) were obtained. The lysosomal genes associated with distant metastasis were screened by least absolute shrinkage and selection operator(LASSO)-based logistic regression. Further the LASSO-based COX regression model was employed to screen the genes closely related to prognosis of colorectal cancer patients. Among those genes, the iduronic acid-2-sulfatase(IDS) was selected because of its largest regression coefficient. Then, 50 paraffin embedded colorectal cancer tissues harvested in our hospital from 2007 to 2008 were used for IDS immunohistochemistry staining. The relationships of IDS expression level in the tissues with metastasis and prognosis of colorectal cancer were analyzed. Results The results of TCGA database analysis showed that the relative mRNA expression level of IDS was significantly higher in the colorectal cancer patients with lymph node metastasis than those without(N0 vs N1-2:-0.103±0.073 vs 0.303±0.123, P=0.003), and was much higher in those with distant metastasis than those without(M0 vs M1: 0.017±0.071 vs 0.636±0.296, P=0.003);and the patients with high expression of IDS had poor prognosis(overall survival: P=0.008;disease-free survival: P=0.007). COX regression analysis indicated that the mRNA expression of IDS was an independent predictors of colorectal cancer prognosis(P=0.014, Hazard ratio=2.651, 95%CI: 1.217~5.775). The results of immunohistochemical analysis for the 50 cases showed that the expression of IDS was higher in colorectal cancer patients with lymph node metastasis than those without(N0 vs N1-3: 27.324±0.698 vs 40.674±3.528, P=3.0×10^-5), and was higher in those with distant metastasis than those without(M0 vs M1: 27.941±0.952 vs 39.320±3.467, P=1.2×10^-5), and the patients with high IDS expression suggested poor pr

关 键 词：艾杜糖醛酸-2-硫酸酯酶 结直肠癌 肿瘤转移 生物信息学 

分 类 号：R345[医药卫生—基础医学] R730.7