Expression of Endogenous Retroviral RNA in Prostate Tumors has Prognostic Value and Shows Differences among Americans of African Versus European/Middle Eastern Ancestry

SIMPLE SUMMARY: Endogenous retroviruses (ERVs) are viral sequences that have been incorporated into the human genome over millions of years via integrations in germ-line cells. In this study, we investigated whether the expression of ERVs was associated with two different aspects of prostate cancer (PCa). First, Black American men have a higher incidence and poorer outcome of PCa compared to White men. We identified differences in ERV expression among prostate tumors between men of primarily African versus primarily European or Middle Eastern ancestry, which may be associated with differences in the mechanism of cancer progression in patients of these distinct ancestries. Second, we determined whether ERV expression might be correlated with the progression of disease, regardless of ancestry. We identified the ERV expression signatures that correlated with biochemical relapse among PCa patients of all ancestries, indicating that ERVs may be useful for identifying cancer patients at greatest risk of progression. The utility of ERV expression for studying cancer progression may extend to other cancers. ABSTRACT: Endogenous retroviruses (ERVs) are abundant, repetitive elements dispersed across the human genome and are implicated in various diseases. We investigated two potential roles for ERVs in prostate cancer (PCa). First, the PCa of Black Americans (BA) is diagnosed at an earlier median age and at a more advanced stage than the PCa of White Americans (WA). We used publicly available RNA-seq data from tumor-enriched samples of 27 BA and 65 WA PCa patients in order to identify 12 differentially expressed ERVs (p(adj) < 0.1) and used a tissue microarray of the PCa cores from an independent set of BA and WA patients to validate the differential protein expression of one of these ERVs, ERV3-1 (p = 2.829 × 10(−7)). Second, we used 57 PCa tumors from patients of all ancestries from one hospital as a training set to identify the ERVs associated with time to biochemical relapse. A 29-ERV prognostic panel was then tested and validated on 35 separate PCa tumors from patients obtained in two different hospitals with a dramatic increase in prognostic power relative to clinical parameters alone (p = 7.4 × 10(−11)). In summary, ERV RNA expression differences in the prostate tumors of patients of different ancestries may be associated with dissimilarities in the mechanism of cancer progression. In addition, the correlation of expression of certain ERVs in prostate tumors with the risk of biochemical relapse indicates a possible role for ERV expression in cancer progression.