血浆外泌体脂多糖结合蛋白对结直肠癌早期诊断及进展监测价值分析  

Value of plasma exosomal lipopolysaccharide-binding protein in early diagnosis and progression monitoring of colorectal cancer

作　　者：李蕾[1,2] 李光浩 郑白冰 王世文 谢丽 LI Lei;LI Guanghao;ZHENG Baibing;WANG Shiwen;XIE Li(School of Medical Laboratory,Weifang Medical University,Weifang 261053,China;Key Laboratory of Radiation Oncology,Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan 250117,China)

机构地区：[1]潍坊医学院医学检验学院,山东潍坊261053 [2]山东省肿瘤防治研究院(山东省肿瘤医院)放射肿瘤学重点实验室,山东第一医科大学(山东省医学科学院),山东济南250117

出　　处：《中华肿瘤防治杂志》2023年第16期964-971,共8页Chinese Journal of Cancer Prevention and Treatment

基　　金：山东省自然科学基金(ZR2020LZL017,2019YFF0216502)。

摘　　要：目的 寻找对结直肠癌具有理想诊断效能的敏感且特异的微创生物标志物。方法 应用蛋白质印迹法及酶联免疫吸附试验(ELISA)分析2021-07-30-2021-12-31山东省肿瘤医院收治的224例结直肠癌患者(包括117例早期患者)与210名健康志愿者血浆外泌体脂多糖结合蛋白(LBP)的表达差异。使用SPSS 26.0分析LBP作为诊断标志物的灵敏度和特异度。通过Wilcoxon符号秩检验分析配对样本LBP浓度与手术的关系。采用Spearman相关性分析判断LBP不同表达浓度与患者发生肝转移以及血液学指标是否存在关系。结果 蛋白质印迹法及ELISA验证均发现结直肠癌患者血浆外泌体LBP表达水平高于健康志愿者,均P<0.001。受试者工作特征(ROC)曲线结果显示,外泌体LBP对结直肠癌与早期结直肠癌的诊断效能分别为0.871和0.861,联合癌胚抗原(CEA)、糖类抗原19-9(CA19-9)后诊断结直肠癌及早期结直肠癌的AUC值分别为0.879和0.846。相较于未发生转移的患者,发生肝转移的结直肠癌患者外泌体LBP水平更高(P<0.001),联合CEA后对肝转移的诊断效能为0.863。去除肿瘤后2周内,血液学指标血小板/淋巴细胞比值(PLR,r_(s)=0.506,P<0.01)、中性粒细胞/淋巴细胞比值(NLR,r_(s)=0.533,P<0.01)水平与患者血浆外泌体LBP水平呈正向相关关系,均表现为水平上调,均P<0.001;而淋巴细胞/单核细胞比值(LMR,r_(s)=-0.325,P=0.031)与LBP水平呈负向相关关系,出现水平下调,P<0.001。结论 血浆外泌体LBP可以作为结直肠癌尤其是早期结直肠癌的新型诊断标志物,可以用于临床监测肿瘤进展。Objective To find sensitive and specific minimally invasive biomarkers with ideal diagnostic efficacy in colorectal cancer.Methods The differences in the expression of plasma exosomal lipopolysaccharide-binding protein(LBP) between224 colorectal cancer patients(including 117 early-stage) and 210 healthy donors were confirmed by using Western blot and enzyme-linked immunosorbent assay(ELISA).By using SPSS 26.0,the sensitivity and specificity of LBP as a diagnostic marker were examined.The Wilcoxon signed-rank test was used to investigate the association between LBP levels and operation in matched samples.On the basis of Spearman correlation analysis,it was decided whether there was a connection between various LBP expression concentrations and the occurrence of liver metastases and hematological indicators in patients.Results The expression of plasma exosomal LBP was found to be higher in colorectal cancer patients compared to healthy volunteers(P<0.001) by both Western blot and ELISA validation,and the diagnostic efficacy of exosomal LBP for colorectal cancer and early colorectal cancer was found to be 0.871 and 0.861,respectively.The AUCs for colorectal cancer and early colorectal cancer after combining carcinoembryonic antigen(CEA) and carbohydrate antigen19-9(CA19-9) were 0.879 and 0.846,respectively by establishing the receiver operating characteristic(ROC) curve.Compared with patients without metastasis,exosomal LBP levels were higher in colorectal cancer patients with liver metastasis(P<0.001),and the diagnostic efficacy for liver metastasis after combining CEA was 0.863.The levels of the hematological indicators platelet/lymphocyte ratio(PLR,r_s=0.506,P<0.01) and neutrophil/lymphocyte ratio(NLR,r_s=0.533,P<0.01) showed a positive correlation with the level of exosomal LBP in patients' plasma within 2 weeks after tumor removal,both showing an upregulation(P<0.001),while the lymphocyte/monocyte ratio(LMR,r_s=-0.325,P=0.031)showed a negative correlation with the level of LBP,with a down-regulation of levels(P

关 键 词：结直肠癌 生物标志物 外泌体 脂多糖结合蛋白 肝转移 

分 类 号：R735.34[医药卫生—肿瘤]