Detection and characterization of latency stage of EBV and histopathological analysis of prostatic adenocarcinoma tissues

Abstract

The pathophysiology of prostate cancer involves both genetic and acquired factors, including pathogens, such as viruses. A limited number of studies have shown the presence of Epstein-Barr virus (EBV) in prostate cancer tissues. However, there is a dearth of data exploring EBV latency profile in prostate cancer, and the relationship of EBV with histopathological features of prostate cancer. In this study, prostate cancer and benign prostatic hyperplasia (BPH) samples were screened for the presence of EBV, followed by the characterization of the EBV latency profile and analysis of histopathological parameters in EBV-positive and EBV-negative groups. A conventional PCR strategy was employed using virus-specific primers to screen EBV in 99 formalin-fixed paraffin-embedded (FFPE) prostate cancer and 33 BPH samples received for histopathological analysis during the years 2019–2020. Subsequently, cDNA samples were used in a qPCR array to analyze the expression of EBV latency-associated genes to map the latency profile EBV maintains in the samples. Finally, statistical analyses were performed to determine the correlation between EBV and several histopathological features of the samples. EBV was detected in 39% of prostate cancer and 24% of BPH samples. The histopathological analysis of prostate cancer samples identified all samples as prostatic adenocarcinoma of acinar type, while statistical analyses revealed EBV-positive samples to exhibit significantly higher (p < 0.05) Gleason major and total Gleason scores as compared to EBV-negative samples. In the EBV-positive samples, variable expression patterns of latency-associated genes were observed, where most of the samples exhibited EBV latency II/III-like profiles in prostate cancer, while latency-II-like profiles in BPH samples. This study suggests a high prevalence of EBV in prostate samples, where EBV exhibited latency II/III-like profiles. Furthermore, EBV-positive samples exhibited a higher Gleason score suggesting a possible link between EBV and the onset/progression of prostate cancers. However, future functional studies are required to understand the role of the EBV gene expression profile in the onset/progression of prostate cancer.

The Association between Infectious Mononucleosis and Cancer: A Cohort Study of 24,190 Outpatients in Germany

“…To our knowledge, our study was further the first to indicate a strong trend toward an increased risk of prostate cancer associated with infectious mononucleosis, although the corrected level of statistical significance was not reached. The role of EBV in the development and progression of prostate cancer has remained controversial in the literature; however, EBV is reported to be detectable in 40–50% of prostate cancer specimens [ 23 ]. It is suggested that EBV infection with subsequent expression of EBV latency genes could enhance survival of premalignant cells and provide anti-apoptotic properties to epithelial cells in the premalignant stage [ 24 ].…”

Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma

“…Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV) 3 – 5 . Our recent report showed that EBV maintains a latency II/II-like profile in PCa tissues, and EBV-PCR-positive PCa tissues exhibited higher Gleason scores compared to EBV-negative PCa tissues 4 . However, it is not known whether the presence of EBV in PCa tissues is associated with histopathological and gene expression changes associated with cancer aggressiveness.…”

“…Similarly, the alterations in the gene expression of c-Myc, BCL-2, TP53, MDM-2, Rb, BRCA-1, BRCA-2, CDKN-1B, CDKN-1A , and CDKN-1B have shown to be associated with PCa progression 14 , 15 , and EBV has been shown to modulate several of these genes in other cancer types 4 , 16 , however, the EBV-associated dysregulation of gene expression in PCa has not been explored. In addition, certain prostate-specific miRNAs (oncomiRs) reportedly regulate a wide array of prostatic functions, ranging from proliferation to apoptosis.…”

CMV and EBV Co-Infection in HIV-Infected Children: Infection Rates and Analysis of Differential Expression of Cytokines in HIV Mono- and HIV–CMV–EBV Co-Infected Groups

“…Additionally, non-template/non-primer control (NTC/NPC) was included on each plate as a negative control for each primer. This strategy has been optimized previously in our laboratory [32][33][34]. The cytokine expression was determined using the ∆Ct method [35,36].…”