Abstract 5160: Evaluation of circulating microRNAs as predictive and prognostic biomarkers for advanced melanoma patients

Abstract

Abstract Introduction Metastatic melanoma is the deadliest form of skin cancer whose incidence has been rising dramatically over the last few decades. The advent of Immune checkpoint inhibitors (ICIs) has strongly improved the survival of melanoma patients. However, a high fraction of patients shows primary resistance or will develop secondary resistance during therapy. For these reasons, it is of utmost importance to develop biomarkers that could predict response or resistance to therapies. Among the most promising biomarkers analyzed in peripheral blood there are circulating microRNAs (miRNAs). The aim of this study is to identify a miRNA signature able to predict prognosis and clinical relapse in advanced melanoma patients treated with ICIs. Methodology We collected longitudinal blood draws from metastatic melanoma patients treated with ICIs at Bologna University-Hospital (Italy). We separated plasma from whole blood, extracted RNA and determined the absolute levels of miR-155-5p, miR-424-5p and miR-320a using EvaGreen-based droplet digital PCR. Moreover, in the subset of first-line anti-PD-1 treated patients, we performed cytofluorimetric leukocyte analysis. Results and discussion We found that patients with pre-therapy (baseline) high expression of circulating miR-155-5p, miR-320a and mir-424-5p had longer progression-free survival (PFS), and overall-survival (OS). In patients treated with anti PD-1 as first-line treatment, we found that baseline miR-155-5p levels were significantly higher in patients who responded to therapy, and therefore miR-155-5p could have a predictive value. Moreover, using a flow cytometric approach, we noted that baseline miR-155-5p levels correlated with CD4+Naïve (r:-0.91, p:0.027) and CD4+PD1+ T-cells (r:0.94, p:0.015) in patients treated with first-line anti-PD-1 treatment. Conclusion These preliminary findings propose baseline circulating miRNAs as potential predictive and prognostic biomarkers in the setting of advanced melanoma patients treated with immunotherapy. Citation Format: Giorgio Durante, Francesca Comito, Maria Naddeo, Serena De Matteis, Massimiliano Bonafè, Emi Dika, Andrea Ardizzoni, Manuela Ferracin. Evaluation of circulating microRNAs as predictive and prognostic biomarkers for advanced melanoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5160.