Abstract 5605: Cutibacterium acnes invades prostate epithelial cells to induce BRCAness as a possible pathogen of prostate cancer

Abstract Abundant evidence suggests that chronic inflammation is linked to prostate cancer and that infection is a possible cause of prostate cancer. However, pathogen of prostate cancer remains to be found. To identify microbiota or pathogens associated with prostate cancer, we investigated the transcriptomes of 20 human prostate cancer tissues. We performed de novo assembly of non-human sequences from RNA-seq data and identified four bacteria as candidate microbiota in the prostate, including Moraxella osloensis, Uncultured chroococcidiopsis, Cutibacterium acnes, and Micrococcus luteus. Among these, C. acnes was detected in 19 of 20 prostate cancer tissue samples by immunohistochemistry. We then analyzed the gene expression profiles of prostate epithelial cells infected in vitro with C. acnes and found significant alterations in homologous recombination (HR) and Fanconi anemia pathway. Notably, electron microscopy showed that C. acnes invaded prostate epithelial cells and localized in perinuclear vesicles, whereas analysis of γH2AX foci and HR assay demonstrated impaired HR repair. In particular, BRCA2 was significantly down-regulated in C. acnes-infected cells. These findings suggest that C. acnes infection in the prostate could lead to HR deficiency and BRCAness which promotes DNA double-strand breaks, thereby increasing the risk of cancer development. Citation Format: Shingo Ashida, Chiaki Kawada, Hiroko Tanaka, Atsushi Kurabayashi, Ken-ichi Yagyu, Shuji Sakamoto, Kazuhiro Maejima, Satoru Miyano, Masanori Daibata, Hidewaki Nakagawa, Keiji Inoue. Cutibacterium acnes invades prostate epithelial cells to induce BRCAness as a possible pathogen of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5605.