AUTHOR=Cangemi Michela , Zanussi Stefania , Rampazzo Enrica , Bidoli Ettore , Giunco Silvia , Tedeschi Rosamaria , Pratesi Chiara , Martorelli Debora , Casarotto Mariateresa , Martellotta Ferdinando , Schioppa Ornella , Serraino Diego , Steffan Agostino , De Rossi Anita , Dolcetti Riccardo , Vaccher Emanuela 

TITLE=Biological Predictors of De Novo Tumors in Solid Organ Transplanted Patients During Oncological Surveillance: Potential Role of Circulating TERT mRNA

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772348

DOI=10.3389/fonc.2021.772348

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p><italic>De novo</italic> tumors are a major cause of morbidity and mortality after long-term solid organ transplantation. Chronic immunosuppression strongly affects solid organ transplanted (SOT) patients’ immune system by promoting immune evasion strategies and reactivations of viruses with oncogenic potential, ultimately leading to cancer onset. In this scenario, an oncological Surveillance Protocol integrated with biobanking of peripheral blood samples and evaluation of immunovirological and molecular parameters was activated for SOT patients at CRO-IRCCS Aviano, with the aim of identifying suitable biomarkers of cancer development.</p></sec><sec><title>Methods</title><p>An exploratory longitudinal study was designed based on two serial peripheral blood samples collected at least three months apart. Forty nine SOT patients were selected and stratified by tumor onset during follow-up. Spontaneous T-cell responses to EBV, CMV and tumor associated antigens, EBV-DNA and CMV-DNA loads, and circulating <italic>TERT</italic> mRNA levels were investigated.</p></sec><sec><title>Results</title><p>Significantly higher levels of circulating <italic>TERT</italic> mRNA were observed 3.5-23.5 months before and close to the diagnosis of cancer as compared to tumor-free patients. Plasmatic <italic>TERT</italic> mRNA levels &gt;97.73 copies/mL at baseline were significantly associated with the risk of developing <italic>de novo</italic> tumors (HR=4.0, 95%C.I. = 1.4-11.5, p=0.01). In particular, the risk significantly increased by 4% with every ten-unit increment in <italic>TERT</italic> mRNA (HR=1.04, 95%C.I. = 1.01-1.07, p=0.01).</p></sec><sec><title>Conclusions</title><p>Although obtained in an exploratory study, our data support the importance of identifying early biomarkers of tumor onset in SOT patients useful to modulate the pace of surveillance visits.</p></sec>