Abstract

Pancreatic adenocarcinomas (PAADs) often remain undiagnosed until later stages, limiting treatment options and leading to poor survival. The lack of robust biomarkers complicates PAAD prognosis, and patient risk stratification remains a major challenge. To address this issue, we established a panel constructed by four miRNAs (miR-4444-2, miR-934, miR-1301 and miR-3655) based on The Cancer Genome Atlas (TCGA) and Human Cancer Metastasis Database (HCMDB) to predicted the prognosis of PAAD patients. Then, a risk prediction model of these four miRNAs was constructed by using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) regression analysis. This model stratified TCGA PAAD cohort into the low-risk and high-risk groups based on the panel-based risk score, which was significantly associated with 1-, 2-, 3-year OS (AUC=0.836, AUC=0.844, AUC=0.952, respectively). The nomogram was then established with a robust performance signature for predicting prognosis compared to clinical characteristics of pancreatic cancer (PC) patients, including age, gender and clinical stage. Moreover, two GSE data were validated the expressions of 4 miRNAs with prognosis/survival outcome in PC. In the external clinical sample validation, the high-risk group with the upregulated expressions of miR-934/miR-4444-2 and downregulated expressions of miR-1301/miR-3655 were indicated a poor prognosis. Furthermore, the cell counting kit-8 (CCK-8) assay, clone formation, transwell and wound healing assay also confirmed the promoting effect of miR-934/miR-4444-2 and the inhibiting effect of miR-1301/miR-3655 in PC cell proliferation and migration. Taken together, we identified a new 4-miRNA risk stratification model could be used in predicting prognosis in PAAD.Keywords: miRNA, pancreatic adenocarcinoma, risk stratification, prognosis, treatment strategies