HERV-K Gag RNA and protein levels are elevated in malignant regions of the prostate in males with prostate cancer

Heightened expression of human endogenous retrovirus (HERV) sequences has been associated with a range of malignancies, including prostate cancer, suggesting that they may serve as useful diagnostic or prognostic cancer biomarkers. We analysed the expression of HERV-K (Gag and Env/Np9 regions), HERV...

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Hauptverfasser: Rezaei, Simin Dokht (VerfasserIn) , Hayward, Joshua A. (VerfasserIn) , Norden, Sam (VerfasserIn) , Pedersen, John (VerfasserIn) , Mills, John (VerfasserIn) , Hearps, Anna C. (VerfasserIn) , Tachedjian, Gilda (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 10 March 2021
In: Viruses
Year: 2021, Jahrgang: 13, Heft: 3, Pages: 1-12
ISSN:1999-4915
DOI:10.3390/v13030449
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/v13030449
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1999-4915/13/3/449
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Verfasserangaben:Simin D. Rezaei, Joshua A. Hayward, Sam Norden, John Pedersen, John Mills, Anna C. Hearps and Gilda Tachedjian

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520 |a Heightened expression of human endogenous retrovirus (HERV) sequences has been associated with a range of malignancies, including prostate cancer, suggesting that they may serve as useful diagnostic or prognostic cancer biomarkers. We analysed the expression of HERV-K (Gag and Env/Np9 regions), HERV-E 4.1 (Pol and Env regions), HERV-H (Pol) and HERV-W (Gag) sequences in prostate cancer cells lines and normal prostate epithelial cells using qRT-PCR. HERV expression was also analysed in matched malignant and benign prostate tissue samples from men with prostate cancer (n = 27, median age 65.2 years (range 47-70)) and compared to prostate cancer-free male controls (n = 11). Prostate cancer epithelial cell lines exhibited a signature of HERV RNA overexpression, with all HERVs analysed, except HERV-E Pol, showing heightened expression in at least two, but more commonly all, cell lines analysed. Analysis of primary prostate material indicated increased expression of HERV-E Pol but decreased expression of HERV-E Env in both malignant and benign regions of the prostate in men with prostate cancer as compared to those without. Expression of HERV-K Gag was significantly higher in malignant regions of the prostate in men with prostate cancer as compared to matched benign regions and prostate cancer-free men (p < 0.001 for both), with 85.2% of prostate cancers donors showing malignancy-associated upregulation of HERV-K Gag RNA. HERV-K Gag protein was detected in 12/18 (66.7%) malignant tissues using immunohistochemistry, but only 1/18 (5.6%) benign tissue sections. Heightened expression of HERV-K Gag RNA and protein appears to be a sensitive and specific biomarker of prostate malignancy in this cohort of men with prostate carcinoma, supporting its potential utility as a non-invasive, adjunct clinical biomarker. 
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