MicroRNA signatures of cancer risk in kidney transplant patients: insights from the COMETA study

Background: Post-transplant malignancies are one of the leading causes of morbidity, mortality and graft failure in kidney transplant recipients (KTRs). While viral infections and immunosuppressive drugs have historically been considered primary causes, the mechanisms underlying post-transplant cancer occurrence remain incompletely understood. Furthermore, predictive cancer biomarkers have yet to be identified in KTRs. Methods: COMETA study is an observational study involving 138 KTRs, and it aims to elucidate the interplay between the immune system and cancer by integrating comprehensive clinical data with high-throughput small-RNA sequencing on the serum of patients with post-kidney transplant malignancies. Results: Our results identified three distinct serum miRNA profiles, respectively, associated with kidney transplantation, pro-oncogenic and onco-protective factors in this unique population. These profiles were also used to create miRNA classifiers, which demonstrated promising predictive performance, especially for tumor-promoting signatures. Notably, miR-210-3p up-regulation, within the cancer-related profile was first found to be associated with non-melanoma skin cancer. Conclusion: These findings could serve as a basis for future research, paving the way for the development of advanced tools for early cancer diagnosis, precise prognosis formulation, and the creation of targeted therapies for KTRs with neoplastic complications.