Abstract: FR-OR067
The COMETA Study: A systems biology approaCh to the mOlecular (miRNA) profiling of the nEoplastic risk in kidney TransplAnt recipients
Session Information
- Transplantation: Basic Science Innovations and Advances
November 07, 2025 | Location: Room 370A, Convention Center
Abstract Time: 05:00 PM - 05:10 PM
Category: Transplantation
- 2101 Transplantation: Basic
Authors
- Alfieri, Carlo, Universita degli Studi di Milano, Milan, Lombardy, Italy
- Simeoni, Mariadelina, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Campania, Italy
- Grandinetti, Valeria, IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola, Bologna, Emilia-Romagna, Italy
- La Manna, Gaetano, IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola, Bologna, Emilia-Romagna, Italy
- Castellano, Giuseppe, Universita degli Studi di Milano, Milan, Lombardy, Italy
- Capasso, Giovambattista, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Campania, Italy
Background
Post-transplant malignancies significantly contribute to morbidity, mortality, and graft loss in kidney transplant recipients (KTRs). Traditional risk factors include viral infections and immunosuppressive medications; however, the molecular mechanisms remain incompletely understood. Predictive biomarkers for cancer development in KTRs are urgently needed.
Methods
The multicentric COMETA study evaluated serum microRNA (miRNA) profiles from 138 KTRs using high-throughput sequencing. Differentially expressed miRNAs were identified through pairwise comparisons among pre-transplant, post-transplant without cancer, and post-transplant with cancer patient groups. Functional enrichment analyses and validation of cancer-associated miRNAs were performed using TCGA cohort data.
Results
Our analyses revealed three distinct miRNA profiles associated respectively with transplant-related (TR), pro-oncogenic (CR), and cancer-protective (CP) conditions. Significant differential miRNA expression included 67 miRNAs altered in post-transplant patients with cancer versus pre-transplant patients, 146 altered in post-transplant patients without cancer versus pre-transplant patients, and 38 significantly altered between post-transplant patients with and without cancer. The CR-profile uniquely included miR-210-3p, significantly upregulated and identified for the first time in association with non-melanoma skin cancers (NMSC), alongside three downregulated miRNAs (miR-1-3p, miR-10b-5p, miR-30a-3p). Classifiers based on generalized linear models using the CR-profile achieved an area under the curve (AUC) of 0.781, demonstrating predictive potential. Functional enrichment analysis indicated that miRNAs from the CR-profile significantly modulated biological processes related to the inflammasome pathway (NLRP3) and interleukin signaling (IL-2, IL-6, IL-27), processes implicated in tumor initiation and immune responses. Validation using TCGA data supported differential expression patterns across various cancers.
Conclusion
MiRNA profiles, particularly miR-210-3p, hold promise for early cancer detection, prognosis stratification, and targeted therapeutic strategies in KTRs, highlighting their potential clinical utility.