Autor: |
Monastirioti A; Laboratory of Translational Oncology, School of Medicine, University of Crete, Vassilika Vouton, 71003 Heraklion, Crete, Greece., Papadaki C; Laboratory of Translational Oncology, School of Medicine, University of Crete, Vassilika Vouton, 71003 Heraklion, Crete, Greece., Kalapanida D; Department of Medical Oncology, University General Hospital of Heraklion, Vassilika Vouton, 71110 Heraklion, Crete, Greece., Rounis K; Laboratory of Translational Oncology, School of Medicine, University of Crete, Vassilika Vouton, 71003 Heraklion, Crete, Greece.; Thoracic Oncology Center, Theme Cancer, Karolinska University Hospital, 17164 Stockholm, Sweden.; Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden., Michaelidou K; Laboratory of Translational Oncology, School of Medicine, University of Crete, Vassilika Vouton, 71003 Heraklion, Crete, Greece., Papadaki MA; Laboratory of Translational Oncology, School of Medicine, University of Crete, Vassilika Vouton, 71003 Heraklion, Crete, Greece., Mavroudis D; Laboratory of Translational Oncology, School of Medicine, University of Crete, Vassilika Vouton, 71003 Heraklion, Crete, Greece.; Department of Medical Oncology, University General Hospital of Heraklion, Vassilika Vouton, 71110 Heraklion, Crete, Greece., Agelaki S; Laboratory of Translational Oncology, School of Medicine, University of Crete, Vassilika Vouton, 71003 Heraklion, Crete, Greece.; Department of Medical Oncology, University General Hospital of Heraklion, Vassilika Vouton, 71110 Heraklion, Crete, Greece. |
Abstrakt: |
Since circulating microRNAs (miRNAs) are involved in the modulation of the immune response, they are tested as liquid biopsy-based biomarkers in patients with NSCLC treated with immunotherapy. We analyzed the expression levels and examined the clinical significance of immunoregulatory miRNAs involved in immune checkpoint regulation (miR-34a, miR-200b, miR-200c), T-cell activity (miR-155), and the function of myeloid-derived suppressive cells (MDSCs) (miR-223) or regulatory T lymphocytes (Tregs) (miR-146a), in patients with advanced NSCLC (N = 69) treated with anti-PD-1 (Nivolumab) immunotherapy as 2nd or 3rd line of treatment therapy. Plasma levels of circulating miRNAs were analyzed by RT-qPCR before the initiation of immunotherapy. Expression of miR-34a, miR-146a, mir-200c, and miR-223 was found to be associated with response to immunotherapy. High miR-200c expression emerged as an independent prognostic factor for inferior overall survival in all patients with NSCLC (OS, HR: 2.243, 95% CI: 1.208-4.163; p = 0.010) and in patients with non-Squamous (non-SqCC) subtype (N = 38) (HR: 2.809, 95% CI: 1.116-7.074; p = 0.028). Low miR-34a expression independently predicted for shorter OS (HR: 3.189, 95% CI: 1.193-8.527; p = 0.021) in the non-SqCC subgroup. Our findings suggest that alterations in circulating miR-200c and miR-34a expression levels are associated with the response and outcome in patients with advanced NSCLC treated with anti-PD1 immunotherapy. |