Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer

SIMPLE SUMMARY: While the intratumor microbiome has been largely unexplored in relation to prostate cancer development, our research shows that microbes may play an anti-tumor or pro-tumor role to significantly alter clinical course in prostate cancer patients. We found that the presence and absence of specific microbes are strongly correlated with known biomarkers of prostate cancer, including increased androgen receptor expression, prostate-specific antigen level, immune-associated gene dysregulation, stem-cell related gene overexpression, cancer pathways, and known chromosomal alterations. Our results provide important insight on potential mechanisms by which intratumor microbes may greatly contribute to prostate cancer progression and prognosis. We hope our results can be validated in future studies, and the key microbes that we identified can be used as effective targets for more specialized prebiotic and probiotic treatments for prostate cancer. ABSTRACT: Although 1 in 9 American men will receive a diagnosis of prostate cancer (PC), most men with this diagnosis will not die from it, as most PCs are indolent. However, there is a subset of patients in which the once-indolent PC becomes metastatic and eventually, fatal. In this study, we analyzed microbial compositions of intratumor bacteria in PC to determine the influence of the microbiome on metastatic growth. Using large-scale RNA-sequencing data and corresponding clinical data, we correlated the abundance of microbes to immune pathways and PC risk factors, identifying specific microbes that either significantly deter or contribute to cancer aggressiveness. Interestingly, most of the microbes we found appeared to play anti-tumor roles in PC. Since these anti-tumor microbes were overrepresented in tumor samples, we believe that microbes thrive in the tumor microenvironment, outcompete cancer cells, and directly mitigate tumor growth by recruiting immune cells. These include Listeria monocytogenes, Methylobacterium radiotolerans JCM 2831, Xanthomonas albilineans GPE PC73, and Bradyrhizobium japonicum, which are negatively correlated with Gleason score, Tumor-Node-Metastasis (TNM) stage, prostate-specific antigen (PSA) level, and Androgen Receptor (AR) expression, respectively. We also identified microbes that contribute to tumor growth and are positively correlated with genomic alterations, dysregulated immune-associated (IA) genes, and prostate cancer stem cells (PCSC) genes.