Circulating miRNAs as Non-Invasive Biomarkers in Pancreatic Cancer: A Two-Phase Plasma-Based Study

<b>Background/Objectives:</b> MiRNAs have demonstrated promising roles in the diagnosis of pancreatic cancer and in the prognostic assessment of affected patients. <b>Methods:</b> We conducted a prospective pilot study including 23 patients diagnosed with advanced-stage pancreatic cancer and 10 healthy controls, matched by age and sex. In the screening phase, we evaluated the expression of 176 miRNAs in pooled plasma samples from both groups using real-time PCR. Subsequently, we validated the overexpression of selected miRNAs in individual plasma samples using the same technique. Statistical analysis was performed using IBM SPSS Statistics version 29. <b>Results:</b> During the screening phase, 22 miRNAs exhibited differential expression in patients with pancreatic cancer compared to healthy controls. Among these, hsa-miR-100-5p (27.8-fold increase), hsa-miR-122-5p (7.5-fold), hsa-miR-885-5p (7.2-fold), hsa-miR-34a-5p (5.7-fold), and hsa-miR-193a-5p (4.4-fold) showed the most pronounced upregulation. In the validation phase, all five candidates demonstrated significant overexpression in individual plasma samples (<i>p</i> < 0.001). Their circulating levels also showed associations with tumor stage (<i>p</i> < 0.05). <b>Conclusions:</b> Our findings highlight a distinct circulating miRNA signature associated with advanced pancreatic cancer, supporting the potential role of hsa-miR-100-5p, hsa-miR-122-5p, hsa-miR-885-5p, hsa-miR-34a-5p, and hsa-miR-193a-5p as minimally invasive biomarkers for disease detection and staging. Larger, multicenter studies including early-stage patients and disease control groups will be required to validate these biomarkers and determine their clinical utility.