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Intestinal Bacteria: Biomarkers and Targets for Colorectal Cancer

By Parker Lynch

According to a study published in Cancer Biology & Medicine, the role of intestinal bacteria in the development of colorectal cancer (CRC) has been receiving a lot of attention in recent years. Various bacteria such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, Enterococcus faecalis, and Salmonella sp., have been known to cause DNA damage. Additionally, these bacteria also help tumor cells evade the body’s immune response, creating a pro-inflammatory environment. The DNA damage and other hindrances upon one’s immune system and bodily function have been associated with the development and progression of CRC.

These bacteria can be useful biomarkers for CRC. Additionally, progress is being made in developing effective antibacterial therapies, which could prove useful in the treatment of CRC.

Parker Lynch is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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Could Blood-based Testing Improve CRC Screening Barriers?

By Parker Lynch

Despite the current methods that exist for people to receive preventative screenings, colorectal cancer (CRC) screening rates remain below the 80% national goal. Since the utilization of the current testing methods are subpar among average-risk adults in America, researchers are testing the reliability of a blood-based test, which remains a preferable screening method for a variety of preventive tests in the general population. The hope is that a preferred screening method would improve screening rates for CRC among average-risk adults. 

Testing the Reliability and Validity of a Blood-Based Test

The ECLIPSE clinical trial evaluated the performance of a cell-free DNA blood-based CRC screening test. Individuals who were average-risk (those with no identifiable risk factors or abnormal predispositions to being diagnosed with CRC), 45 years of age or older, and presenting for colonoscopy screening were recruited from 265 U.S. clinical sites between October 2019 and September 2022. This population was diverse, which makes the findings generalizable:

  • 54% female
  • 7% Asian
  • 12% Black/African-American 
  • 79% white
  • 12% Hispanic/Latino 

Prior to their colonoscopy, participants provided whole blood samples. In doing so, researchers were able to compare the validity of the blood-based tests when compared to the actual results that were obtained from the colonoscopy procedures. 

The trial found that the blood test was:

  • 90% sensitive to detecting Stage I – III CRC
  • 100% sensitive to detecting Stage IV CRC
  • 90% specific

In another study, researchers retrospectively analyzed blood samples of 425 individuals who were to undergo a colonoscopy. The blood samples were tested for specific genetic and epigenetic changes and these were then correlated with the individual’s colonoscopy results. 

Here’s a fun video that explains what genetic and epigenetic changes are.

The test was found to be:

  • 82% sensitive for CRC
  • 90% specific

Overall, the researchers concluded that this test provides clinically meaningful performance and has utility for CRC screening.  A limitation of the specificity/sensitivity study was the utilization of an older version of the assay. However, should the results of up-to-date versions of the assay remain statistically significant, blood-based screening could be a very effective and preferable CRC screening method. 

Both these studies demonstrate the effectiveness of blood-based tests, which will hopefully improve the rate at which people get their preventative testing for CRC.

 

Parker Lynch is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

 

Photo credit: Photo by Testalize.me on Unsplash  

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Inflammatory Biomarkers Can Predict Colorectal Cancer Recurrence and Mortality 

Interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-a) are inflammatory biomarkers that are capable of activating Janus kinase signaling pathways, nuclear factor signaling pathways, and C-reactive protein (CRP) transcription. CRP tests are commonly used in cancer care to predict prognosis, as activation of the Janus kinase and nuclear factor signaling pathways can  aid in tumor expansion and metastasis. Additionally, high-sensitivity CRP tests (hsCRP) are able to identify small amounts of CRP in blood samples.

One recent study assessed the association between these inflammatory biomarkers (IL-6, TNF-a, and hsCRP) with CRC recurrence and mortality in 1,494 stage III colorectal cancer (CRC) patients. This was the largest study assessing the relationship between these inflammatory biomarkers and CRC survival as of yet. 

While the study recruited a diverse sample of individuals, the final sample was overwhelmingly White (82.3%) and non-Hispanic (94.5%). Future studies should prioritize racial diversity to more accurately assess this association, as racial disparities exist in CRC diagnoses and outcomes. 

Researchers collected plasma samples from participants 3-8 weeks following their surgery but prior to chemotherapy. These plasma samples were then analyzed for IL-6, TNF-a, and hsCRP. The primary study outcome was disease-free survival and secondary outcomes were recurrence-free survival and overall survival. Participants who had higher concentrations of IL-6, TNF-a, and hsCRP were more likely to have CRC recurrence. High levels of these biomarkers were also found to be associated with an increased risk of mortality.

This study reveals that there is a significant association between inflammation following stage III diagnosis and poor CRC outcomes. Clinicians can utilize this information to better monitor their patients and improve CRC outcomes with evidence-based treatment solutions.

Emma Edwards is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

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