An overall aim of the project is to define immuno-microbial signatures that can be used for non-invasive detection of colorectal cancer and pre-cancer stages.
A link between microbes and some forms of cancer is now generally acknowledged.
However, much remains to be done before we understand how microorganisms contribute to the development of cancer and how we can use this knowledge in cancer prevention.
In the last decade, intestinal bacteria (collectively: microbiota) have been linked to colorectal cancer (CRC), and increased levels of specific bacteria have been detected in colorectal tumors.
Whether the microbiota has a role in development of cancer or whether they occur secondarily has not yet been clarified, although there are studies that support both theories.
To understand the role of the microbiota in CRC, it is necessary to study how they affect the surrounding tissue in various stages of cancer development.
We are thus investigating the local immune response in colorectal tumors and adenomatous polyps, with the aim of correlating specific bacterial populations with unique immune profiles.
The main project is owned and managed by Akershus University Hospital.
Participants
More about the project
Two PhD projects are using different approaches to reach the overall aim of the project.
Their working titles are:
- Exploring Fusobacterium spp. as non-invasive biomarkers for colorectal cancer screening
- Circle – Immune profiles in colorectal cancer
We have detected increased levels of bacteria originating from the oral cavity in colorectal tumors. Several of these microbes are known biofilm formers in the oral cavity, e.g., Fusobacterium nucleatum.
Biofilms are structured bacterial communities of bacteria that are attached to each other and to a solid surface.
Our preliminary results show that the tumor-associated bacteria are found in low abundance in feces compared to the tumor, which may indicate that they have a strong adhesion to the tumor and mucosa.
Biofilm formation in the tumor and the intestinal mucosa could be a contributing factor to this. Most colorectal tumors develop from adenomatous polyps, although only approximately 10 percent of polyps develop into cancer.
Mapping bacterial profiles in polyps can indicate whether the tumor-associated bacteria in question are already present at the polyp stage and clarify their role in cancer development.
It is known that the immune response has an important role in the development of colorectal cancer, but it is less known when the various immune responses are activated, and which changes that occur at the adenomatous polyp stage.
Through mapping of immune gene expression and mapping of bacterial profiles at various stages, we believe that the study will contribute to a better understanding of the interaction between bacteria, the immune response and cancer.
We aim to define specific immune-microbiological signatures that can be used as biomarkers for the non-invasive detection of colorectal cancer and pre-cancer stages.
Experimental approach
Through collaboration with Akershus University Hospital (Ahus), we have used samples from a well characterized biobank at Ahus.
The biobank consists of samples from patients with colorectal cancer, patients with adenomatous polyps and healthy controls.
Through Next Generation sequencing of the gene for 16S rRNA in bacteria, as well as targeted quantitative PCR analyses, we have mapped the bacteria in tumors, adenomatous polyps and healthy intestinal mucosa, as well as from feces samples.
To map the immune response in tumor tissue, we have analyzed RNA with a combination of the nCounter system from Nanostring Technologies (nCounter Analysis Systems for Biomarker Validation & Development) and traditional RT-qPCR analyses.
nCounter is based on color-coded molecular probes hybridizing to specific mRNA molecules in the sample, before the complexes are immobilized on streptavidin-coated surfaces/arrays.
Main findings
Results from the study have so far shown that a group of biofilm-associated bacteria is increased in tumors and other positions in the gut in cancer patients compared to patients with polyps and healthy controls.
These include bacteria in the genera Fusobacterium, Gemella, Pravimonas, Granulicatella and Peptostreptococcus.
On the tumor itself, Fusobacterium nucleatum is highly increased in several patients. We have detected the same bacteria in faeces.
Using qPCR-based protocols developed during the project, we identified several assays that could distinguish between cancer patients, polyp patients and healthy controls.
We suggest that these assays should be tested on a larger selection of fecal samples to investigate their potential in a non-invasive screening.
