Assessing genetic and oncobiome profiles of patients with NMIBC: A transcriptomic analysis.

Abstract

e16589 Background: Non-muscle invasive bladder cancer (NMIBC) has a high propensity for recurrences. Demographic and environmental factors can alter the native oncobiome of the bladder, which may influence tumorigenesis. This study aimed to characterize the genetic profile of the tumor and understand the pathways by which oncobiome could influence tumor behavior. Methods: A prospective study was conducted of patients undergoing transurethral bladder resection for NMIBC. Cold-cup biopsies were taken from the tumor site and the adjoining healthy bladder site. Shotgun sequencing was performed from the extracted ribosomal-depleted RNA. A transcriptomic analysis assessed differential host gene expression and microbiome profile between tumor and normal bladder mucosa. Results: Twelve samples from 6 patients were processed for analysis. All patients had a solitary bladder mass < 3 cm and were from similar socio-economic backgrounds. Following filtration for ≥ log2 fold change, 57 genes were selected, with 45 downregulated and 12 upregulated. 30 of these genes, including TMEM119 and DCN, belonged to extracellular matrix pathways, thus suggesting a matrix-regulating role in carcinogenesis. Following filtration, 37 operational taxonomic units (OTUs) were retained at the species level and used for all microbiome analyses. Alpha diversity indices showed statistically significant differences in species richness between tumor and normal groups (12.2±6.01 vs. 21.5±5.96, p = 0.026). Propionibacterium acnes had a relative abundance of 23.9% in tumor sites and 13% in normal mucosa across all samples, implying a pro-tumor effect. Similarly, Prevotella copri displayed 12.7% and 1.7% abundance in the normal and tumor groups. Bifidobacterium longum had a greater abundance in the normal site (3.9%) compared to the tumor site (0.84%) with incidence rates of 66.7% and 33.3% respectively. In microbial-gene interactions, 80 correlations were statistically significant between 18 microbes and 45 genes. Corynebacterium durum and Veillonella dispar showed the strongest gene correlations, particularly extracellular matrix genes. TMEM119 was linked to the highest number of microbes, including B. longum , Bacillus flexus and Faecalibacterium prausnitzii being negatively associated and Prevotella stercorea and Streptococcus luticiae being positively associated. Conclusions: Our findings emphasized a predominantly extracellular matrix-related tumor invasion, with interactions suggesting oncobiome to play a crucial role in this process. P. acnes , previously implicated in prostate cancer, also exhibited a tumor-promoting role in NMIBC. B.longum , widely known as an anti-cancer microbe, was suggested to carry anti-tumor effects. Further studies are needed to explore the mechanistic pathways of interaction and the effect of tumor microenvironment in influencing growth and invasion.