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Exploration of predictive factors based on oral and intestinal bacterial flora for treating patients with urothelial carcinoma

ABSTRACT: Purpose The role of intestinal flora in carcinogenesis and chemotherapy efficacy has been increasingly studied; however, comparisons between oral and intestinal flora remain limited. This study aimed to identify the microbial changes in urothelial carcinoma (UC) by analyzing oral saliva and stool samples from healthy individuals and patients. We also examined the association between microbial composition and immune checkpoint inhibitor (ICI) response. Methods A total of 20 healthy individuals and 38 patients with UC were analyzed. Among them, 27 patients with UC underwent ICI treatment. Oral saliva and stool samples were analyzed for 16S rRNA sequences to assess bacterial composition. Operational taxonomic units were generated, and phylogenetic analysis was performed using the 16S Metagenomics app whithin the Illumina BaseSpace Sequence Hub. Results Patients with UC showed higher Veillonellaceae and Prevotellaceae levels in saliva and stool, with lower levels of these bacteria associated with more prolonged overall survival and progression-free survival, particularly Veillonellaceae in stool. A higher neutrophil-to-lymphocyte ratio correlated with increased levels of these bacteria. Conclusion Veillonellaceae and Prevotellaceae are potential microbial biomarkers of survival outcomes and ICI efficacy in patients with UC. Non-invasive oral microbial sampling may facilitate personalized cancer treatment strategies.

ORGANISM(S): human oral metagenome human gut metagenome

PROVIDER: GSE293354 | GEO | 2025/05/28

REPOSITORIES: GEO

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Project description:Background: The differential abundance of cell-free RNAs in bodily fluids is emerging as a promising tool for the non-invasive molecular diagnosis of cancer. Human saliva is considered a promising source of non-invasive biomarkers of diagnostic value for oral cancer detection. This study aims to identify diagnostic potent salivary RNAs in oral squamous cell carcinoma (OSCC)-patients by RNA-Sequencing. Method: Unstimulated saliva was collected from 5 normal control (NC) individuals and 9 OSCC patients (PS) with prior consent and ethical committee approvals. Total RNA isolated from cell-free saliva (CFS) supernatant was used to prepare small RNA libraries and sequenced on the Ion Torrent S5 platform. The sequencing reads were aligned to the human genome (hg19) using Bowtie 2, and the differential expression analysis was performed using RUVSeq and DESeq2. Mapped reads were screened across miRBase (v22) annotations for miRNAs and Gencode (v19) annotation for other RNAs. Reads were quantified by the Featurecount (v1.4.6) module of the R-package. The microbial-RNA enrichment analysis was determined using the One Codex platform. Result: RNA-sequencing detected protein-coding transcripts (PCTs), long-intergenic RNAs (lincRNAs), microRNAs (miRNAs), small nuclear RNAs (snRNAs), transfer RNAs (tRNAs) and pseudogenes from the saliva of PS and HC samples. Transcriptome analyses revealed 89 PCTs, 18 lincRNAs and 6 miRNAs differentially expressed between PS and HC with a log2fold change ≥ 1 or ≤ -1 and p-value < 0.05. Gene ontology and pathway enrichment analyses indicated a significant correlation of the identified PCTs and miRNAs to various cancer-related pathways that may have implications in the pathogenesis of OSCC. Interestingly, unmapped non-human reads aligned to the microbial reference genomes. Further analyses of these microbial sequence reads revealed a significant microbial dysbiosis differentiating PS from HC. Metabolic pathways and functional analysis of the identified microbial phylotypes showed gene ontologies associated with inflammation, cell proliferation, ROS generation, and a range of metabolic processes. Conclusion: We report novel panels of differentially expressed PCTs, miRNAs and lincRNAs distinguishing PS from HC. Importantly, our results also provide evidence for oral microbial dysbiosis that appears to have pathological implications in OSCC. Summarily, this study provides a comprehensive landscape of salivary RNAs that can be exploited as non-invasive biomarkers for OSCC detection.

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Exploration of predictive factors based on oral and intestinal bacterial flora for treating patients with urothelial carcinoma

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