Location and condition based reconstruction of colon cancer microbiome from human RNA sequencing data

Abstract

Background The association between microbes and cancer has been reported repeatedly; however, it is not clear if molecular tumour properties are connected to specific microbial colonisation patterns. This is due mainly to the current technical and analytical strategy limitations to characterise tumour-associated bacteria. Methods Here, we propose an approach to detect bacterial signals in human RNA sequencing data and associate them with the clinical and molecular properties of the tumours. The method was tested on public datasets from The Cancer Genome Atlas, and its accuracy was assessed on a new cohort of colorectal cancer patients. Results Our analysis shows that intratumoural microbiome composition is correlated with survival, anatomic location, microsatellite instability, consensus molecular subtype and immune cell infiltration in colon tumours. In particular, we find Faecalibacterium prausnitzii, Coprococcus comes, Bacteroides spp., Fusobacterium spp. and Clostridium spp. to be strongly associated with tumour properties. Conclusions We implemented an approach to concurrently analyse clinical and molecular properties of the tumour as well as the composition of the associated microbiome. Our results may improve patient stratification and pave the path for mechanistic studies on microbiota-tumour crosstalk.

The value of intratumoral microbiota in the diagnosis and prognosis of tumors

“…This association may suggest a link to the chronic progression of gastrointestinal diseases toward colon cancer, making it a potential marker for early diagnosis 43 . In addition, accumulated palmitic acid, a metabolite produced by ITM, has been implicated in shaping the immunosuppressive environment of the TME, especially mast cells, dendritic cells, and other cells susceptible to stimulation, suggesting that ITM‐derived metabolites may serve as detectable indicators of tumor development 44 …”

“…43 In addition, accumulated palmitic acid, a metabolite produced by ITM, has been implicated in shaping the immunosuppressive environment of the TME, especially mast cells, dendritic cells, and other cells susceptible to stimulation, suggesting that ITM-derived metabolites may serve as detectable indicators of tumor development. 44 The enrichment of PDAC with microorganisms linked to the onset of oral or intestinal diseases, including Campylobacter spp., F. nucleatum, and Leptospira, is consistent with the findings of previous studies identifying microorganisms associated with pancreatic and gastrointestinal diseases. These microorganisms play a role in tumor development and impact the prognosis of immunotherapy by influencing immunity, particularly T cells involved in immunotherapy responses.…”

“…ITM, such as Aspergillus, Actinomyces, Firmicutes, and bacteria in thyroid cancer may be distinguished from the surrounding healthy tissue. 44 The ITM Clostridium perfringens and Staphylococcus spp. are more predominant in nasopharyngeal carcinoma than that in healthy tissues.…”

“…As the study of ITM progresses, an increasing number of tumors have a “bacterial” presence, and these ITM play a role within the tumor (Table 2). ITM, such as Aspergillus, Actinomyces, Firmicutes , and bacteria in thyroid cancer may be distinguished from the surrounding healthy tissue 44 . The ITM Clostridium perfringens and Staphylococcus spp.…”