上海交通大学学报（医学版）2025，Vol.45Issue(10)：1342-1352,11.DOI:10.3969/j.issn.1674-8115.2025.10.009
COL12A作为一种新型的胰腺导管腺癌血清诊断标志物的鉴定与评价
Identification and evaluation of COL12A1 as a novel serological diagnostic marker in pancreatic ductal adenocarcinoma
摘要
Abstract
Objective·To identify and evaluate novel and reliable non-invasive serological biomarkers for detecting pancreatic ductal adenocarcinoma(PDAC).Methods·Sixty-seven PDAC patients(Ruijin cohort Ⅰ)were recruited at Pancreatic Center,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from May 2018 to December 2019.Global proteome profiling of 67 PDAC tumor tissues and 67 matched adjacent normal tissues was performed using mass spectrum.Bioinformatics analysis on the proteomics data was conducted to identify new biomarkers,and receiver operating characteristic(ROC)curves and the area under the curve(AUC)were used to evaluate their value of detecting PDAC.The proteomic and mRNA sequencing data were further downloaded and analysed from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)cohort for validation.In addition,the Ruijin Cohort Ⅱ,consisting of 47 PDAC patients and 75 healthy individuals,was recruited for a case-control study from June 2021 to June 2022.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression level of new biomarkers in the serum of patients and healthy individuals to evaluate the serological diagnostic values of them.Results·Collagen type Ⅻ α1 chain(COL12A1)was identified as a candidate biomarker for PDAC diagnosis based on differential expression analysis on the proteomic data and was validated to be higher in tumor tissues than in adjacent normal tissues in the CPTAC cohort.In addition,COL12A1 protein levels were significantly higher in the sera of PDAC patients than in those of healthy controls,showing good diagnostic performance with an AUC of 0.82,a sensitivity of 81%,and a specificity of 83%.ROC analysis revealed that COL12A1 improved the performance of carbohydrate antigen 199(CA199)in distinguishing PDAC patients from healthy individuals(AUCCA199=0.91 vs AUCCA199+COL12A1=0.95,P<0.05).Furthermore,COL12A1 also showed excellent ability to distinguish early-stage PDAC patients(stage Ⅰ‒Ⅱ)from healthy individuals(AUCCOL12A1=0.83),and significantly improved the AUC of CA199 in early-stage PDAC patients(AUCCA199=0.92 vs AUCCA199+COL12A1=0.97,P<0.05).Conclusion·COL12A1 is a potential serological diagnostic marker that complements CA199 in detecting early-stage PDAC.关键词
胰腺导管腺癌/胶原蛋白Ⅻ型α1链/糖类抗原199/诊断/蛋白质组学Key words
pancreatic ductal adenocarcinoma(PDAC)/collagen type Ⅻ α1 chain(COL12A1)/carbohydrate antigen 199(CA199)/diagnosis/proteome分类
医药卫生引用本文复制引用
刘佳,任灵杰,施敏敏,唐笑梅,马芳芳,秦洁洁..COL12A作为一种新型的胰腺导管腺癌血清诊断标志物的鉴定与评价[J].上海交通大学学报（医学版）,2025,45(10):1342-1352,11.基金项目
国家自然科学基金(82304212). National Natural Science Foundation of China(82304212). （82304212）
