Epstein-Barr Virus and Human Adenovirus Viremia in Renal Tumors Is Associated with Histological Features of Malignancy

Abstract

Background: There is growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic/latent viral infections with the clinical course of renal cell carcinoma (RCC). Methods: In this prospective study we enrolled 27 patients undergoing partial or radical nephrectomy due to the histologically confirmed RCC and followed them up for one year post-operation. Isolation of the nucleic acids was performed using the NucleoSpin Tissue Kit (Macherey-Nagel, Düren, Germany) from tumor tissue and using the EZ1 Virus Mini Kit v2.0 from plasma. The number of viral copies of human adenovirus (ADV), herpes simplex virus HSV-1 and HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK virus (BKV) and John Cunningham virus (JCV) in the tissue and plasma was assessed with real-time PCR. Results: Viral infections were diagnosed in ten patients (37.0%), including three ADV cases (11.1%) and eight EBV cases (29.6%). Infected patients tended to be significantly older (71.3 vs. 57.6 years, p < 0.05), more commonly presented with chronic renal disease (OR 2.4, p < 0.05), diabetes (OR 4.2, p < 0.05) and overweight (OR 2.0, p < 0.05). Regarding oncological data, infected patients were found to have a higher rate of high-grade cancers (OR 5.0, p < 0.05) and a higher rate of papillary RCCs (OR 8.3, p < 0.05). Status of viral infections had no influence on the clinical cancer stage, surgical procedure or survival. Conclusions: EBV and ADV infections are common in renal cancer patients and increase the risk of high-grade RCC presence. While there is no significant impact on short term survival, further studies are needed to assess the relevance of these findings in a long run.

Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning

“…Moreover, we found the viral transcription and viral gene expression pathways were upregulated in subtype 3 and downregulated in subtype 2, suggesting that these two subtypes' molecular characteristics may be associated with virus infection. It has been reported that the infection of hepatitis C virus, Epstein-Barr virus and human adenovirus viremia is associated with the development of kidney cancer ( Hofmann et al., 2011 ; Kryst et al., 2020 ; Wu et al., 2021 ). The downregulated genes in subtype 3 were significantly enriched in fatty acid metabolism-related pathways such as fatty acid catabolic procession and fatty acid oxidation.…”

“…The upregulated genes in subtype 3 were significantly enriched in the translational initiation and protein localization to ER pathways, which showed an opposite character to subtype 2 (Figure 3E). Moreover, we found the viral transcription and viral gene expression pathways were upregulated in subtype 3 and downregulated in subtype 2, suggesting that these two subtypes' molecular characteristics (Hofmann et al, 2011;Kryst et al, 2020;Wu et al, 2021). The downregulated genes in subtype 3 were significantly enriched in fatty acid metabolism-related pathways such as fatty acid catabolic procession and fatty acid oxidation.…”

Epstein–Barr virus infection is associated with the nuclear factor-kappa B p65 signaling pathway in renal cell carcinoma

“…This finding is in line with a study by Shimakage et al on 9 RCC cases and 2 RCC cell lines, all of which were found to be infected with EBV [ 12 ]. The frequency of EBV infection in RCC tumors was reported to be 15.6% and 29.6% in two other former studies [ 13 , 14 ]. Our results, along with the others’, show that EBV infection is common in RCCs.…”

“…In addition, the expression of EBV nuclear antigen 2 (EBNA2) in renal tubule cells has been reported to induce renal tumors in transgenic mice [ 11 ]. Furthermore, there are accumulating data available suggesting a role for EBV in RCC pathogenesis [ 12 – 14 ]. Together, these findings not only suggest that renal tissue is a likely reservoir of EBV, but also imply the oncogenic potential of EBV in the renal tissue.…”

Epstein-Barr virus, human cytomegalovirus, human herpesvirus 6 and 7, human adenovirus, John Cunningham virus, and BK virus are not associated with gliomas in humans

“…The method was previously described. 14 Viral nucleic acids were isolated from plasma using EZ1 Virus Mini Kit v2.0 (Qiagen, Hilden, Germany) according to the manufacturer's instructions with a BioRobot EZ1 device (Qiagen, Hilden, Germany). Quality and quantity control was done using an ND-1000 spectrophotometer (NanoDrop Technologies, Wilmington, Delaware, USA).…”