In the oncological area, pancreatic cancer is one of the most lethal diseases, with 5-year survival rising just 10% in high-development countries. This disease is genetically characterized by KRAS as a driven mutation followed by SMAD4, CDKN2, and TP53-associated mutations. In clinical aspects, pancreatic cancer presents unspecific clinical symptoms with the absence of screening and early plasmatic biomarker, being that CA19-9 is the unique plasmatic biomarker having specificity and sensitivity limitations. We analyzed the plasmatic exosome proteomic profile of 23 patients with pancreatic cancer and 10 healthy controls by using Nanoscale liquid chromatography coupled to tandem mass spectrometry (NanoLC-MS/MS). The pancreatic cancer patients were subdivided into IPMN and PDAC. Our findings show 33, 34, and 7 differentially expressed proteins when comparing the IPMN vs. control, PDAC-No treatment vs. control, and PDAC-No treatment vs. IPMN groups, highlighting proteins of the complement system and coagulation, such as C3, APOB, and SERPINA. Additionally, PDAC with no treatment showed 11 differentially expressed proteins when compared to Folfirinox neoadjuvant therapy or Gemcitabine adjuvant therapy. So here, we found plasmatic exosome-derived differentially expressed proteins among cancer patients (IPMN, PDAC) when comparing with healthy controls, which could represent alternative biomarkers for diagnostic and prognostic evaluation, supporting further scientific and clinical studies on pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide, largely because it is diagnosed late. Diagnosis typically relies on imaging and biopsy, but only after tumors have advanced, which reduces treatment effectiveness. Current biochemical biomarkers are limited to CA19-9, which is more useful for prognosis and monitoring than for diagnosis. Circulating miRNAs may offer minimally invasive complementary biomarkers for PDAC diagnosis, potentially accounting for ethnic and treatment-related variables. We performed small RNA sequencing on plasma from five non-metastatic-stage and five metastatic-stage PDAC patients and 10 healthy controls to generate an exploratory miRNA profile. Candidate miRNAs were then validated by RT-qPCR in an independent cohort of 70 PDAC patients and 106 healthy controls, and nine miRNAs showed promising differential plasma expression. Notably, miRNA484 and miRNA335-5p were associated with PDAC in CA19-9-negative patients, with ROC AUCs of 0.984 and 0.88, respectively. Overall, these results indicate that miRNA484 and miRNA335-5p may have clinical value as complementary biomarkers for PDAC patients who are CA19-9-negative.