Abstract
BackgroundWith over 350,000 estimated deaths worldwide in 2018, prostate cancer (PCa) continues to be a major health concern and a significant cause of cancer-associated mortality among men. While cancer in general is considered a disease of the human genome, there is a growing body of evidence suggesting that changes to the healthy microbiota could play a vital role in cancer development, progression, and/or treatment outcome.MethodsUsing a metatranscriptomic approach, we annotated the microbial reads obtained from total RNA sequencing of 106 prostate tissue samples from 94 PCa patients (discovery cohort). We investigated microbial dysbiosis associated with PCa by systematically comparing the microbiomes between benign and malignant tissue samples, between less vs. more-aggressive PCa, and between patients who had biochemical recurrence as opposed to those who did not. We further performed differential gene expression and cell type enrichment analysis to explore the host transcriptomic and cellular responses to selected microbial genera. A public dataset (GSE115414) of total RNA sequencing reads from 24 prostate tissue samples (8 benign and 16 malignant) served as the validation cohort.ResultsWe observed decreased species diversity and significant under-representation of Staphylococcus saprophyticus and Vibrio parahaemolyticus, as well as significant over-abundance of Shewanella in malignant as compared to benign prostate tissue samples in both the discovery (p < 0.01) and validation (p < 0.05) cohorts. In addition, we identified Microbacterium species (p < 0.01) to be significantly over-abundant in pathologically advanced T3 tumors compared to T2 in the discovery cohort. Malignant samples having high vs. low Shewanella counts were associated with downregulated Toll-like receptor signaling pathways and decreased enrichment of dendritic cells. Malignant samples having low vs. high V. parahaemolyticus counts were enriched for olfactory transduction and drug metabolism pathways. Finally, malignant samples were enriched for M1 and M2 macrophages as compared to benign tissue samples.ConclusionsThe results from this exploratory study support the existence of an important biological link between the prostate microbiota and PCa development/progression. Our results highlight Shewanella, V. parahaemolyticus, and Microbacterium sp. as interesting candidates for further investigation of their association with PCa.
Highlights
With over 350,000 estimated deaths worldwide in 2018, prostate cancer (PCa) continues to be a major health concern and a significant cause of cancer-associated mortality among men
We systematically compared microbial species associations with more/less aggressive PCa using key clinicopathological factors known to be associated with PCa aggressiveness as well as post-operative biochemical recurrence (BCR) status (Table 1, Additional file 1: Fig. S1)
Shewanella genera might be associated with malignant transformation of the prostate tissue that could be facilitated by a decreased host immune response
Summary
With over 350,000 estimated deaths worldwide in 2018, prostate cancer (PCa) continues to be a major health concern and a significant cause of cancer-associated mortality among men. Few earlier and smaller-scale studies investigating microbial signatures in benign and malignant prostate tissue have found some evidence to support a PCa-specific microbiota [10, 11]. It has been reported that prostate tumor tissue from African patients might harbor different microbial loads compared to Australian patients [13]. All these studies support the existence of a non-sterile prostate microenvironment
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