Description:
Bacterial gene-associated methods and compositions for diagnosing and treating colorectal cancer
The present disclosure provides compositions and non-invasive methods for diagnosing a subject at risk for developing, or having, or at risk for progressing on colorectal cancer (CRC) based on analysis of bacterial species in the gut microbiome of the subject. This helps determine the appropriate treatment or management plan for these patients.
Colorectal cancer (CRC) is one of the most common cancers globally. While epidemiological and disease cohort studies implicate a link between gut microbiomes and CRC, specific gut microbes appear to be causative in a small minority of CRC cases and estimated effect sizes are modest. Fred Hutchinson Cancer Center researchers hypothesized that CRC risk is shaped by the cumulative effects of multiple diverse gut microbes, including bacteria not previously recognized. Our researchers have conducted a large-scale meta-analysis of published microbiome surveys and identified microbial marker genes that identify bacteria that are consistently observed at higher or lower abundance in CRC patients across four independent global cohorts. During in vivo validation studies, the cancer-associated consortium designed with these marker genes induced greater tumor burden in a preclinical mouse model of CRC. Thus, the identified cancer-associated microbial marker genes can be used as a microbiome-based, non-invasive risk profiling and screening tool for CRC.
<ul>
<li>Identifies the subject as being at-risk for developing or progressing on CRC</li>
<li>Helps determine management or treatment plan (For e.g., performing colonoscopy vs increase frequency of colonoscopies vs prescribing NSAID or polyp removal/ colon resection surgery etc.)</li>
</ul>
<ul>
<li>Non-invasive (i.e., uses fecal samples), cost-effective and better sensitivity than Fecal Immunochemical Test (FIT)</li>
<li>Amenable to development of at-home collection kits and easy to integrate with existing workflows (i.e., residual sample from FITs sufficient to profile and score the microbiome)</li>
</ul>
American Cancer Society estimated CRC to be the fourth most diagnosed and second deadliest cancer in the U.S. (in men and women combined). The majority of CRC cases presently cannot be linked to hereditary or familial drivers; however, disproportionate CRC burden is suffered by minority communities including Black Americans and Alaska Natives. Current screening strategies include colonoscopy, Cologuard™ and FIT. While effective, these tests are imperfect (e.g., invasiveness, sub-optimal sensitivity and /or false negative/positive rates). Thus, in addition to the existing tests, there is a public health need for non-invasive, but high-sensitivity, lower cost clinical tools that enable greater uptake and increased screening rates, thereby decreasing CRC-related mortality.
<ul>
<li> Neelendu Dey, MD Assistant Professor - Translational Science and Therapeutics Division.</li>
<li> Sam Minot, PhD. Staff Scientist - Microbiome Research Initiative, Vaccine and Infectious Disease Division; Associate Director, Data Science Applications</li>
</ul>
Preclinical <em>in vitro</em>, Preclinical <em>in vivo</em>
US Non-provisional filed, patent pending
22-207_Dey_CRC Microbiome_NCS_FHCC.pdf
Colorectal cancer | microbiome | gut | bacteria| | co-abundant genes (CAG) | sub-species | gene clustering | metagenome | Cologuard | FIT | colonoscopy | CRC surveillance | polyp | non-invasive | fecal | stool sample | microbial marker genes |
CRC Microbiome_NCS_22-207