Pilot validation of a whole-blood mRNA expression-based diagnostic system for early-stage pancreatic ductal adenocarcinoma: a single-center case-control diagnostic accuracy study.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis because most cases are diagnosed at an advanced stage. We previously developed a whole-blood messenger RNA (mRNA) expression-based diagnostic system using 56 genes, but its performance in very early-stage PDAC remains unclear. This single-center prospective pilot study evaluated the diagnostic accuracy of the mRNA-based system in patients with stage 0-I PDAC. Among 253 patients diagnosed between 2020 and 2024, ten with stage 0 or I disease were included. One hundred and four healthy controls were analyzed for comparison. Whole blood samples were analyzed by reverse transcription polymerase chain reaction, and a pre-specified locked algorithm generated an mRNA diagnostic score. Serum carbohydrate antigen 19 - 9 (CA19-9) was evaluated using a cut-off of 37 U/mL. The mRNA-based system detected 9 of 10 early-stage PDAC cases (sensitivity 90.0%; 95% CI 55.5-99.8%), whereas CA19-9 detected 1 of 10 (10.0%; 95% CI 2.5-44.5%). Specificity was 70.2% for the mRNA-based system and 97.1% for CA19-9. The area under the receiver operating characteristic curve was 0.84 and 0.66, respectively. These exploratory findings suggest that whole-blood transcriptomic signatures may improve diagnostic classification of highly selected patients with stage 0-I PDAC. Larger multicenter studies are required to confirm clinical utility.