Biomarkers Mark the Way for Earlier Colon Cancer Diagnosis

By: Karina A. Baksh

Diagnosing the stage and type of cancer is a complex process and varies with each cancer. Some types of cancer – such as colon, cervical, and breast – have organized screening programs to detect cancer at an early stage when it is easier to treat.

Although colon cancer is the second most common cancer in Canada, recent statistics from the Canadian Cancer Society have revealed that 49% of colon cancers are diagnosed at a late stage (Stage III or IV). How is this possible? Unfortunately, it is difficult to make a list of reasons because cancer is complicated and there are many factors that affect screening and diagnosis.

The two main ways to screen for colon cancer are: 1) a colonoscopy, and 2) a stool or fecal test. Stool tests can be done at home using a kit, but have lower specificity and are less sensitive than colonoscopies. Therefore, a colonoscopy might also be done after a stool test to confirm its results. Unfortunately, there are low participation rates for screening by healthy individuals’, making early diagnosis more difficult, likely because people are hesitant to undergo invasive colonoscopies.

Screening guidelines also depend on your risk for a particular cancer. For people considered to be at an average risk, the screening tests are recommended after the person turns 50 years old. However, through personal experience, I have learned that it is possible for someone at an average risk AND under the age of 50 to be diagnosed with stage IV colon cancer. But, as terrifying as that sounds, there is hope for the future.

There is ongoing research into identifying biomarkers that are highly specific, are directly associated with particular cancers, and can be obtained non-invasively through bodily fluids such as blood or urine.

What is a biomarker?

A biomarker is a biological molecule or substance naturally found in the body (such as DNA, RNA, proteins, and metabolites) that can indicate the presence of a particular cancer. Measuring changes in these biomarkers can help doctors diagnose the type and stage of cancer, as well as the effectiveness of a treatment.

A simple way to think of biomarkers is to think of markers that we use to colour. Imagine you have a large box of markers in all the colours of the rainbow. One day when you open the box, you notice all the red markers at the bottom of the box are dry and can no longer be used, but every other colour is fine. The dry red markers indicate something happened to your box, just as a change in a specific substance in the body can indicate a particular cancer.

The nature of a given biomarker can be quite diverse. Just as some colouring markers are permanent and some are washable, some biomarkers are specifically used for diagnosis and monitoring cancer progression, while others are used to predict how well the cancer responds to a particular treatment.

Recent Advances in Biomarker Research

There is a lot of ongoing research into discovering new biomarkers, as well as re-evaluating known biomarkers to determine which are the most specific for colon cancer. Researchers are analyzing samples from patients to identify changes in substances that specifically occur in the presence of colon cancer. For instance, a group of researchers from John Hopkins University recently discovered a protein called β-1,4-GalT-V (β-1,4-galactosyltransferase-V) that is increased in human colon cancer tumors compared to normal tissue. Changes in the amount of this protein can be determined non-invasively from liquid biopsies, and could potentially be used for early detection of colon cancer. The researchers believe that in addition to improved diagnosis, this biomarker is a strong therapeutic candidate for monitoring disease progression.

Research has also shown that measuring changes in more than one biomarker provides more reliable results. Therefore, measuring changes in β-1,4-GalT-V, along with other biomarkers known to be associated with colon cancer, offers a novel strategy for earlier colon cancer detection.

Aside from protein biomarkers, there are well known DNA and RNA biomarkers that can be measured from stool or blood. The discovery of biomarkers that can be measured from stool has been promising because it makes the stool test more sensitive for detecting colon cancer. As more research into biomarkers is done, it becomes more likely that they will become widely used in the clinic, increasing the availability of non-invasive options for being screened.

The future is bright for earlier diagnosis of colon cancer. In Canada, the organized screening program for colon cancer was implemented across most of the country in 2017. The screening program is designed to encourage people between the ages of 50 to 74 that are not at a high risk for colon cancer to participate in screening by sending them invitations to screen, reminders, and notifications of results. Since the screening program is fairly new, it is likely that the percentage of people diagnosed at a late stage will decrease in the upcoming years. In addition, ongoing biomarker research offers new hope for discovering novel treatments for the future.

Karina Baksh is a PhD candidate at the University of Toronto. She is investigating structural biology of a protein that could act as a drug target for treating Helicobacter pylori bacterial infections in the human stomach, which are the main cause of gastric cancer.

 

References

1. Canadian Cancer Statistics Advisory Committee. Canadian Cancer Statistics 2018. Canadian Cancer Society (2018).
2. Recommendations on screening for colorectal cancer in primary care. Can. Med. Assoc. J. 188, 340 LP-348 (2016).
3. Secretan, B. L., Vilahur, N., Bianchini, F., Guha, N. & Straif, K. The IARC Perspective on Colorectal Cancer Screening. N. Engl. J. Med. 378, 1734–1740 (2018).
4. Zarkavelis, G. et al. Current and future biomarkers in colorectal cancer. Ann. Gastroenterol. 30, 613–621 (2017).
5. Chatterjee, S. B. et al. Lactosylceramide synthase β-1,4-GalT-V: A novel target for the diagnosis and therapy of human colorectal cancer. Biochem. Biophys. Res. Commun. 508, 380–386 (2019).
6. Fung, K. Y. C. et al. Blood-based protein biomarker panel for the detection of colorectal cancer. PLoS One 10, 1–11 (2015).
7. Yu, J. et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 66, 70–78 (2017).
8. Goossens, N., Nakagawa, S., Sun, X. & Hoshida, Y. Cancer biomarker discovery and validation. Transl. Cancer Res. 73, 389–400 (2015).
9. Bhangu, A. et al. Novel biomarkers for patient stratification in colorectal cancer: A review of definitions, emerging concepts, and data. World J. Gastrointest. Oncol. 10, 145–158 (2018).