Identification of COL12A1 as a novel diagnostic marker in pancreatic ductal adenocarcinoma by global proteome analysis

Abstract

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive carcinoma without reliable non-invasive screening tests. This study aimed to identify and evaluate novel and reliable noninvasive serological biomarkers for screening PDAC. Methods: We performed global proteome profiling of 67 PDAC tumor tissues and 67 matched normal adjacent tissues by mass spectrum to identify new biomarker in Ruijin cohort 1. This is further verified in proteome and mRNA sequencing data in published cohort by CPTAC. Next, COL12A1 and CA199 serological levels were determined in 47 PDAC sera and 75 healthy sera by enzyme immunoassay in Ruijin cohort 2. Results: Finally, collagen type XII alpha 1 chain (COL12A1) was identified as a candidate for PDAC diagnosis in Ruijin cohort 1, and was validated to be higher in tumor tissues than the normal adjacent tissues (NATs) in CPTAC cohort. In addition, COL12A1 protein was significantly higher in case sera than control sera. The ROC analysis revealed that COL12A1 improved the performance of CA199 in discriminating PDAC from healthy individuals (AUCCA199 = 0.91 vs AUC CA199 + COL12A1 = 0.95, p < 0.05). COL12A1 also showed perfect ability to distinguish early-stage PDAC from healthy individuals (AUCCOL12A1 = 0.83), and was observed to significantly improve AUC of CA199 in stage I-II PDAC (AUCCA199 = 0.92 vs AUCCA199+COL12A1 = 0.97, p < 0.05). Conclusion: This study reveals that COL12A1 is a potential serological diagnostic marker that complements CA199 in detecting early-stage PDAC. It is necessary for a large-scale study to validate the results.