Research Paper Volume 12, Issue 8 pp 7585—7602
PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma
- 1 Clinical Pathology Unit and Center of Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto 71122, Foggia, Italy
- 2 Urology and Renal Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
- 3 Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
- 4 Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto 71122, Foggia, Italy
- 5 Urology and Renal Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto 71122, Foggia, Italy
Received: February 17, 2020 Accepted: March 31, 2020 Published: April 28, 2020
https://doi.org/10.18632/aging.103169How to Cite
Copyright © 2020 Netti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Pentraxin-3 (PTX3) belongs to the pentraxine family, innate immune regulators involved in angiogenesis, proliferation and immune escape in cancer. Here, we evaluated PTX3 tissue expression and serum levels as biomarkers of clear cell renal cell carcinoma (ccRCC) and analyzed the possible role of complement system activation on tumor site. A 10-year retrospective cohort study including patients undergoing nephrectomy for ccRCC was also performed. PTX3 expression was elevated in both neoplastic renal cell lines and tissues, while it was absent in both normal renal proximal tubular cells (HK2) and normal renal tissues. Analysis of complement system activation on tumor tissues showed the co-expression of PTX3 with C1q, C3aR, C5R1 and CD59, but not with C5b-9 terminal complex. RCC patients showed higher serum PTX3 levels as compared to non-neoplastic patients (p<0.0001). Higher PTX3 serum levels were observed in patients with higher Fuhrman grade (p<0.01), lymph node (p<0.0001), and visceral metastases (p<0.001). Patients with higher PTX3 levels also showed significantly lower survival rates (p=0.002). Our results suggest that expression of PTX3 can affect the immunoflogosis in the ccRCC microenvironment, by activating the classical pathway of CS (C1q) and releasing pro-angiogenic factors (C3a, C5a). The up-regulation of CD59 also inhibits the complement-mediated cellular lysis.