Plasma Exosome-Derived microRNAs as Potential Diagnostic and Prognostic Biomarkers in Brazilian Pancreatic Cancer Patients

Abstract

Pancreatic cancer represents one of the leading causes of oncological death worldwide. A combination of pancreatic cancer aggressiveness and late diagnosis are key factors leading to a low survival rate and treatment inefficiency, and early diagnosis is pursued as a critical factor for pancreatic cancer. In this context, plasma microRNAs are emerging as promising players due to their non-invasive and practical usage in oncological diagnosis and prognosis. Recent studies have showed some miRNAs associated with pancreatic cancer subtypes, or with stages of the disease. Here we demonstrate plasma exosome-derived microRNA expression in pancreatic cancer patients and healthy individuals from Brazilian patients. Using plasma of 65 pancreatic cancer patients and 78 healthy controls, plasma exosomes were isolated and miRNAs miR-27b, miR-125b-3p, miR-122-5p, miR-21-5p, miR-221-3p, miR-19b, and miR-205-5p were quantified by RT-qPCR. We found that miR-125b-3p, miR-122-5p, and miR-205-5p were statistically overexpressed in the plasma exosomes of pancreatic cancer patients compared to healthy controls. Moreover, miR-205-5p was significantly overexpressed in European descendants, in patients with tumor progression and in those who died from the disease, and diagnostic ability by ROC curve was 0.86. Therefore, we demonstrate that these three microRNAs are potential plasma exosome-derived non-invasive biomarkers for the diagnosis and prognosis of Brazilian pancreatic cancer, demonstrating the importance of different populations and epidemiological bias.

Keywords: Brazil; exosome; microRNA; pancreatic cancer.

Figure 1

Nano tracking analysis of plasma exosomes isolated from healthy individuals and pancreatic cancer patients. (A) Concentration average of exosome population observed between control group and pancreatic cancer patients. (B) Average size of exosome population observed between control group and pancreatic cancer patients. (C) Comparation of population concentration profile exosome plasma, from control group and pancreatic cancer patients (A,B). The results were analyzed by t-test, comparing the plasmas of patients with the control. (* p ≤ 0.05). EV: extracellular vesicle.

Figure 2

Relative microRNA expression comparison between pancreatic cancer and healthy control groups. miR-125b-3p*, miR-122-5p**, and miR-205-5p*** were expressed significantly higher in pancreatic cancer groups than healthy control groups (* p <0.0001; ** p = 0.0121; *** p = 0.0091).

Figure 3

The upper graphics represent ROC curves of miR125b-3p, 122-5p, and 205-5p for overall pancreatic cancer and healthy controls, with AUC values of 0.736, 0.726, and 0.829, respectively. The lower graphics represent ROC curves of miR125b-3p, 122-5p, and 205-5p only for adenocarcinoma pancreatic cancer and healthy controls with AUC values of 0.782, 0.814, and 0.857.