Yotsutsuji, S.; Kataoka, H.; Ando, T.; Inada, M.; Sugano, M.; Takada, M.; Esaki, M.; Kato, K.; Yamamoto, Y.; Sano, Y.

Background: For pancreatic cancer, practical blood-based tests for early detection and postoperative surveillance remain elusive. We sought to develop a qPCR-measurable serum microRNA (miRNA) panel that robustly discriminates pancreatic cancer from non-cancer controls and other malignancies. Methods: We profiled 255 serum miRNAs in batch 1 (n=72) and selected 27 candidates. Candidates were refined in batch 2 (n=552) and cross-batch evaluation was performed with batch 3 (n=391) to derive a miRNA model. Independent validation used batch 4 (n=616). Clinical relevance was assessed in an independent clinical cohort of resection patients with samples obtained preoperatively and at 1 and 12 months postoperatively. Results: The miRNA model trained on batches 2 and 3 achieved an area under the curve (AUC) of 0.91 and 0.83 for pancreatic cancer versus non-cancer controls and non-cancer plus other cancers, respectively, when independently validated in batch 4. Stage-wise AUCs in batch 4 were 0.91 (I), 0.94 (II), 0.86 (III) and 0.90 (IV). In the clinical batch, the score decreased postoperatively (preoperative vs month 1; p<0.01) and was higher in recurrence than non-recurrence (p<0.001). Conclusions: The developed compact miRNA qPCR assay discriminated pancreatic cancer across independent assay batches and showed clinical relevance for postoperative surveillance. Clinical Trial Registration: Not applicable.