Abstract
Numerous studies indicate that resident microbiome exists in urine of healthy individuals and dysbiosis of the urobiome (urinary microbiome) may be associated with pathological conditions. This study was performed to characterize the alterations in urobiome and explore its implications of clinical outcome in male patients with bladder cancer. 62 male patients with bladder cancer and 19 non-neoplastic controls were recruited. The follow-up study cohort included 40 patients who were diagnosed with non-muscle invasive bladder cancer (NMIBC) and underwent transurethral resection of bladder tumor (TURBT). Mid-stream urine samples were collected from all the participants the day before cystoscopy. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We found bacterial richness indices (Observed Species index, Chao1 index, Ace index; all P < 0.01) increased in cancer group when compared with non-neoplastic group, while there were no differences in Shannon and Simpson index between two groups. During a median follow-up time of 12 (5.25–25) months, 5/40 (12.5%)of the patients developed recurrence and no patient suffered from progression to muscle-invasive disease. Species diversity of the microbiome was significantly higher in the recurrence group compared with non-recurrence group in patients with NMIBC after TURBT. The LEfSe analysis demonstrated that 9 genera were increased (e.g., Micrococcus and Brachybacterium) in recurrence group. To our knowledge we report the relative comprehensive study to date of the male bladder cancer urinary microbiome and its relationship to pathogenesis and clinical outcomes. Given our preliminary data, additional studies evaluating the urine microbiome in relation to clinical outcomes are warranted to improve our understanding of tumor recurrence after TURBT.
Highlights
Bladder cancer is the 7th most commonly diagnosed cancer in males (Ferlay et al, 2013)
After total follow-up, 5/40 (12.5%) of the patients developed a recurrence on cystoscopy, but no patient suffered from progression to muscle-invasive disease
In line with previous studies (Wu et al, 2018), we found that the Observed Species index, Chao1 index and Ace index were significantly higher in cancer group when compared with non-cancer group, suggesting a higher degree of bacterial richness in cancer group
Summary
Bladder cancer is the 7th most commonly diagnosed cancer in males (Ferlay et al, 2013). Superficial bladder cancer is characterized by high recurrence rate, with 50%–70% of patients whose bladders are not removed experiencing a relapse within 5 years of treatments (Ainsworth, 2017). Because of costly lifetime surveillance with periodic cystoscopy and relevant recurrence rates, bladder cancer has the highest cost of any cancer when categorized on a per patient basis (Mossanen and Gore, 2014). This significant financial burden on the population and health care system calls for effective bladder cancer prevention and control (Fankhauser and Mostafid, 2018)
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