Investigating bacteria in poor prognosis prostate cancer

Bampalis, Anastasios (2025) Investigating bacteria in poor prognosis prostate cancer. Doctoral thesis, University of East Anglia.

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Abstract

This thesis investigates the relationship between the prostate microbiome and prostate cancer (PCa), building on research of bacteria influence on cancer development and progression. The uncertainty in predicting PCa progression at initial diagnosis highlights the need for more accurate prognostic tests, and research shows that bacterial biomarkers may hold prognostic marker potential.

Analyses of 277 post-digital rectal examination urine samples identified Anaerococcus prevotii, Anaerococcus lactolyticus and Campylobacter ureolyticus as important features linked to PCa risk, and the former two were significantly associated with increasing PCa risk groups. In addition, differentially expressed eukaryotic genes associated with cancer were identified in samples positive for these species.

Bacteria from post-prostatectomy secretions were cultured and sequenced, leading to the identification of nine novel species from the genera Gemella, Pauljensenia and Streptococcus. The genomes of several isolates contained antimicrobial resistance genes and encoded proteins involved in metabolic pathways linked to pathogenicity and cancer progression.

Human host depletion strategies were investigated to improve bacterial detection in clinical samples, including propidium monoazide treatment, fluorescence-activated cell sorting (FACS) and adaptive sampling Nanopore sequencing. FACS paired with shotgun sequencing showed significant host DNA depletion, indicating potential for this method to improve microbial detection in complex clinical samples. Finally, urine samples collected with the home collection kit were screened for two species of bacteria using both qPCR and NanoString nCounter, with 91.6% agreement for detection of bacteria using the two technologies. A method for bacteria screening was selected for future studies.

This work further explored the PCa microbiome and indicated specific bacterial species as potential biomarkers for PCa risk and prognosis. Novel bacteria species with potential functional roles in cancer-related pathways were identified, adding evidence for host-microbe interactions. The development of new tests that incorporate bacterial biomarkers may lead to improved detection of aggressive PCa at initial cancer diagnosis.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Chris White
Date Deposited:	08 May 2025 07:48
Last Modified:	08 May 2025 07:48
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99206
DOI:

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