血清外泌体LINC02163作为结直肠癌远处转移标志物的临床价值  

Clinical value of serum exosomal LINC02163 as a marker for distant metastasis of colorectal cancer

作　　者：董雅琪 王新慧 赵颖慧 王传新 DONG Yaqi;WANG Xinhui;ZHAO Yinghui;WANG Chuanxin(Department of Clinical Laboratory,The Second Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250033,Shandong,China;Shandong Provincial Key Laboratory of Innovation Technology in Laboratory Medicine,Jinan 250033,Shandong,China;Suzhou Research Institute of Shandong University,Suzhou 215123,Jiangsu,China)

机构地区：[1]山东大学第二医院检验医学中心、山东大学齐鲁医学院,山东济南250033 [2]山东省检验医学创新技术重点实验室,山东济南250033 [3]山东大学苏州研究院,江苏苏州215123

出　　处：《山东大学学报（医学版）》2023年第9期19-28,37,共11页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(82202611);山东省自然科学基金(ZR2022QH031);江苏省自然科学基金(BK20220271);山东大学第二医院基本科研基金(2022YP01);中国博士后科学基金(2022M711912)。

摘　　要：目的探究长链非编码RNA(lncRNA)LINC02163与结直肠癌远处转移的相关性及其生物学功能,并评估血清外泌体LINC02163作为远处转移标志物的潜能。方法分析结直肠癌组织转录组数据挖掘差异lncRNAs;结合患者临床病理和人口统计学参数分析LINC02163在结直肠癌患者中的表达特征;通过结直肠癌组织芯片原位杂交(ISH)实验探究LINC02163与患者预后的相关性;构建裸鼠肿瘤转移模型探究LINC02163对SW620细胞体内远处转移的影响;通过透射电镜、纳米颗粒跟踪分析以及Western blotting鉴定结直肠癌患者血清外泌体;通过核糖核酸酶A(RNase A)孵育实验分析血清外泌体LINC02163的稳定性;绘制受试者工作特征(ROC)曲线评估血清外泌体LINC02163识别远处转移结直肠癌的效能。结果通过5个结直肠癌组织转录组数据筛选出在结直肠癌中高表达的LINC02163;TCGA数据分析表明LINC02163的表达与结直肠癌远处转移相关(P<0.05);ISH实验表明LINC02163高表达与患者预后不良相关(P<0.05);裸鼠肿瘤转移模型显示LINC02163敲低抑制SW620细胞体内的远处转移(P=0.05);外泌体表征实验表明成功提取患者血清外泌体;RNase A孵育实验表明血清外泌体LINC02163具有较高的稳定性;ROC分析显示血清外泌体LINC02163识别远处转移结直肠癌的曲线下面积为0.864。结论LINC02163在结直肠癌中高表达且与远处转移相关,血清外泌体LINC02163具有成为远处转移标志物的潜能。Objective To investigate the correlation between long non-coding RNA(lncRNA)LINC02163 and distant metastasis of colorectal cancer and its biological function,and to evaluate the potential of serum exosomal LINC02163 as a marker for distant metastasis.Methods The differential lncRNAs was screened by analyzing the transcriptome data of colorectal cancer tissues.The clinicopathological parameters and demographic parameters of patients were combined to analyze the expression characteristics of LINC02163.The correlation between LINC02163 and prognosis was investigated by in situ hybridization(ISH)in colorectal cancer microarray.The effects of LINC02163 on the distant metastasis of SW620 cells in vivo was investigated by establishing a tumor metastasis model in nude mice.Serum exosomes were identified with transmission electron microscopy,nanoparticle tracking analysis and Western blotting.The stability of serum exosomal LINC02163 was analyzed with RNase A incubation assay.The receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of serum exosomal LINC02163 in the identification of distant metastasis of colorectal cancer.Results The high expression of LINC02163 in colorectal cancer was screened by five colorectal cancer tissue transcriptome data.TCGA data analysis demonstrated that the expression of LINC02163 was associated with distant metastasis of colorectal cancer(P<0.05).ISH assay showed that high expression of LINC02163 was associated with poor prognosis(P<0.05).Tumor metastasis model in nude mice revealed that LINC02163 knockdown inhibited the distant metastasis of SW620 cells in vivo(P=0.05).Experiments involving the characterization of exosomes showed that serum exosomes were effectively extracted.RNase A incubation demonstrated the high stability of serum exosomal LINC02163.ROC analysis indicated that the area under the curve of serum exosomal LINC02163 was 0.864 for distant metastatic colorectal cancer.Conclusion LINC02163 is highly expressed in colorectal cancer and is associated wi

关 键 词：结直肠癌 远处转移 外泌体 长链非编码RNA 标志物 

分 类 号：R735.3[医药卫生—肿瘤]