Identification of a Novel Serological Pancreatic Ductal Adenocarcinoma Autoantibody Biomarker Panel With Diagnostic and Therapeutic Implications

Abstract

Abstract New biomarkers are urgently needed to detect pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and subsequently individualize treatment strategies. Here, we identified a clinically relevant autoantibody (Aab) biomarker combination for the differential diagnosis of PDAC using high-throughput protein microarray technology. We identified the serological Aab profiles of 93 PDAC, chronic pancreatitis (CP), other pancreatic (PC) and prostate cancers (PRC), non-ulcer dyspepsia patients (DYS), and healthy controls (HC) using microarray technology. Identified Aabs were validated in tumour tissue via western blot and immunohistochemistry analyses. Subsequently, identified biomarkers were used to create a custom PDAC protein microarray and the clinical utility of the biomarker panel was tested in a cancer specificity cohort comprising 223 PDAC, PC, PRC, colorectal cancer (CRC), and HC samples. Combinatorial ROC curve analysis on the training cohort run on the CT100 + microarrays identified the most effective biomarker combination as CEACAM1-DPPA2-DPPA3-MAGEA4-SRC-TBPG-XAGE3 with an AUC = 85·0% (SE = 0·828, SP = 0·684). Additionally, differential expression analysis on the samples run on the IMMUNOME™ array identified 4 biomarkers (ALX1-GPA33-LIP1-SUB1) upregulated in PDAC against diseased and healthy controls. Subsequently, the specificity of our 11-biomarker panel was validated against other cancers (PDACvPC – AUC = 70·3%, PDACvCRC – AUC = 84·3%, PDACvPRC – AUC = 80·2%) and healthy controls (PDACvHC – AUC = 80·9%). We identified a clinically relevant and novel, 11-autoantibody PDAC biomarker panel that differentially diagnosed PDAC and anticipate that the oncogenic relevance of the recognized proteins could be a starting point for new therapies in the future.