Identification of Pathogen Signatures in Prostate Cancer Using RNA-seq

Infections of the prostate by bacteria, human papillomaviruses, polyomaviruses, xenotropic murine leukemia virus (MLV)-related gammaretroviruses, human cytomegaloviruses and other members of the herpesvirus family have been widely researched. However, many studies have yielded conflicting and controversial results. In this study, we systematically investigated the transcriptomes of human prostate samples for the unique genomic signatures of these pathogens using RNA-seq data from both western and Chinese patients. Human and nonhuman RNA-seq reads were mapped onto human and pathogen reference genomes respectively using alignment tools Bowtie and BLAT. Pathogen infections and integrations were analyzed in adherence with the standards from published studies. Among the nine pathogens (Propionibacterium acnes, HPV, HCMV, XMRV, BKV, JCV, SV40, EBV, and HBV) we analyzed, Propionibacterium acnes genes were detected in all prostate tumor samples and all adjacent samples, but not in prostate samples from healthy individuals. SV40, HCMV, EBV and low-risk HPVs transcripts were detected in one tumor sample and two adjacent samples from Chinese prostate cancer patients, but not in any samples of western prostate cancer patients; XMRV, BKV and JCV sequences were not identified in our work; HBV, as a negative control, was absent from any samples. Moreover, no pathogen integration was identified in our study. While further validation is required, our analysis provides evidence of Propionibacterium acnes infections in human prostate tumors. Noted differences in viral infections across ethnicity remain to be confirmed with other large prostate cancer data sets. The effects of bacterial and viral infections and their contributions to prostate cancer pathogenesis will require continuous research on associated pathogens.