The Onset of Post-Transplant Malignancies Is Related to a Change in Gene Expression Profiles in Peripheral Blood Mononuclear Cells

G. Stallone,¹ R. Federica,¹ P. Pontrelli,² M. Accetturo,² A. Oranger,² M. Gigante,² G. Castellano,² A. Schena,² M. Fiorentino,² B. Infante,¹ L. Gesualdo,² G. Grandaliano.¹

¹Dept.of Surgical and Medical Sciences, Nephrology Unit, University of Foggia, Foggia, Italy
²Dept. of Emergency and Organ Transplantation, Nephrology Unit, University of Bari, Bari, Italy.

Meeting: 2015 American Transplant Congress

Abstract number: D29

Keywords: Gene expression, Kidney transplantation, Lymphocyte activation, Post-transplant malignancy

Session Information

Session Name: Poster Session D: Costimulation and Signaling in Lymphocytes

Session Type: Poster Session

Date: Tuesday, May 5, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Malignancies are the third leading cause of death in renal transplant recipients and their incidence is increasing. Although the role of the immune system in malignancies development is known, mechanisms of tumor escape remain an unsolved problem.

Aim of our study was to evaluate differences in gene expression profile of peripheral blood mononuclear cells in transplanted patients with malignancies when compared to controls.

We enrolled 8 patients with post-transplant neoplasia (PTN: 2 kidney graft, 3 native kidney, 2 prostate, 1 bladder), 8 transplanted patients without neoplasia (Tx-control) and 8 non-transplanted patients with cancer (neoplasm control: 4 kidney, 3 prostate,1 bladder). All groups were comparable for the main clinical/demographic features. Transplant patients were all receiving immunosuppressive therapy with calcineurin inhibitors, mycophenolate, steroids. The transcriptomic profiles of peripheral blood mononuclear cells were assessed by microarray. Results were analyzed statistically and functionally (Ingenuity Pathway Analysis). 4355 genes were differentially expressed between PTN and Tx-control. The most significantly represented pathways were ERK/MAPK signaling (p=1.7×10-5), molecular mechanism of cancer (p=1.83×10-4) and PI3K/AKT signaling (p=2.33×10-4). The most significant networks (31<IPA score<25) included regulation of cell cycle and cell signaling, RNA post-transcriptional modification, reparative mechanisms of RNA/DNA, the pathogenesis of immunological and metabolic disorders. The 170 differentially expressed genes between PTN and neoplasm control were included in Erbb2/Erbb3 signaling (p=8.7X10-3), Erbb4 signaling (p=1X10-2), agrin interactions at neuromuscular junction (p=1.46X10-2) and role of p14/p19ARF in tumor suppression (p=2.07X10-2). These genes were included in 12 functional networks involved in inflammatory disease, cellular growth and proliferation and cellular compromise.

Our data, by an “omic” approach, may allow us to identify the immunological mechanisms underlying the development of post-transplant malignancies and suggest new markers useful in the monitoring of transplanted patients

To cite this abstract in AMA style:

Stallone G, Federica R, Pontrelli P, Accetturo M, Oranger A, Gigante M, Castellano G, Schena A, Fiorentino M, Infante B, Gesualdo L, Grandaliano G. The Onset of Post-Transplant Malignancies Is Related to a Change in Gene Expression Profiles in Peripheral Blood Mononuclear Cells [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/the-onset-of-post-transplant-malignancies-is-related-to-a-change-in-gene-expression-profiles-in-peripheral-blood-mononuclear-cells/. Accessed November 21, 2024.

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