中国医学科学院学报2025，Vol.47Issue(6)：910-920,11.DOI:10.3881/j.issn.1000-503X.16558
基于蛋白质组学分析环形交叉轴突导向受体同源物4和原钙黏素12在结直肠癌中筛查、诊断和分期的临床意义
Proteomics-Based Analysis of Clinical Significance of Roundabout Guidance Receptor 4 and Protocadherin 12 in Screening,Diagnosis,and Staging of Colorectal Cancer
摘要
Abstract
Objective To explore the clinical significance of roundabout guidance receptor 4(ROBO4)and protocadherin 12(PCDH12)in the human serum in the screening,diagnosis,and staging of colorectal cancer(CRC)through proteomics and bioinformatics,thus providing a novel screening method with high speci-ficity,sensitivity,and accuracy for the early screening and diagnosis of CRC in clinical practice.Methods Proteomics and bioinformatics approaches were employed to select the target proteins ROBO4 and PCDH12,and the correlation between ROBO4 and PCDH12 was analyzed.A total of 121 CRC patients(cancer group),112 patients with polyps(polyp group),and 108 healthy volunteers(normal group)who received treatment or physical examination from January 2023 to June 2024 were enrolled in this study.ELISA was employed to deter-mine the expression levels of ROBO4,PCDH12,carcinoembryonic antigen(CEA),and carbohydrate antigen 199(CA199)in the samples of each group.The expression levels of the four proteins in the serum were com-pared among the three groups of patients mentioned above,and the relationships of the serum levels of ROBO4 and PCDH12 with the pathological characteristics of the CRC patients were analyzed.Furthermore,the receiver operating characteristic(ROC)curves were established to evaluate the diagnostic efficacy of the serum levels of ROBO4 and PCDH12 for CRC patients in early and progressive stages.Results The target proteins ROBO4 and PCDH12 were screened out through proteomics.Bioinformatics analysis showed that ROBO4 and PCDH12 were highly expressed in CRC patients.Further correlation analysis revealed a positive correlation between ROBO4 and PCDH12 in CRC(R=0.870,P＜0.001).The ELISA results of clinical samples showed that compared with the normal group and polyp group,the cancer group presented elevated expression levels of ROBO4 and PCDH12(all P＜0.001).There was no statistically significant difference in the expression level of ROBO4 or PCDH12 between the normal group and the polyp group(P=0.586,P=0.550).The ROC curves showed that the diag-nostic efficacy of ROBO4,PCDH12,and ROBO4+PCDH12 was 0.787,0.757,and 0.812,respectively,all of which were higher than the diagnostic efficacy of CEA and CA199.Further analysis of serum levels of RO-BO4 and PCDH12 with the pathological data of CRC showed that the serum level of ROBO4 was correlated with differentiation degree(P=0.013),pathological stage(P=0.002),lymph node metastasis(P=0.001),and distant metastasis(P=0.026).The serum level of PCDH12 was correlated with differentiation degree(P=0.043),pathological stage(P=0.012),and lymph node metastasis(P=0.001).The ROC curves showed that the diagnostic efficacy of ROBO4,PCDH12,and ROBO4+PCDH12 was 0.637,0.758,and 0.787 for early CRC and 0.872,0.757,and 0.882 for progressive CRC,respectively.Conclusions The ser-um levels of ROBO4 and PCDH12 demonstrate high diagnostic efficacy for CRC patients and are correlated with the pathological features of CRC.The two proteins are expected to be novel serum biomarkers for the diagnosis and screening of CRC.关键词
结直肠癌/环形交叉轴突导向受体同源物4/原钙黏素 12/诊断效能Key words
colorectal cancer/roundabout guidance receptor4/protocadherin 12/diagnostic efficacy分类
医药卫生引用本文复制引用
FAN Jianchun,CAO Xinran,YANG Chunbaixue,ZHANG Bin,ZHANG Yixuan,XIA Lei,WU Xueliang..基于蛋白质组学分析环形交叉轴突导向受体同源物4和原钙黏素12在结直肠癌中筛查、诊断和分期的临床意义[J].中国医学科学院学报,2025,47(6):910-920,11.基金项目
河北省高层次人才资助项目(A202101062)、2025年河北省在读研究生创新能力培养资助项目(CXZZSS2025119)和河北省国家级大学生创新创业训练项目(202410092006) （A202101062）
