Biomarker testing in colorectal cancer (CRC) informs doctors about unique features of cancer that may influence its growth, spread, recurrence, and treatment response.
Colorectal cancer (CRC), which includes diagnoses of colon cancer and rectal cancer, is cancer that starts in the colon or rectum of your large intestine. It’s a common type of cancer affecting
CRC is treatable, especially when detected early, and doctors can use biomarker testing to enhance your treatment outcomes.
Biomarker testing is a part of
Biomarkers, short for biological markers, are factors and measurable states, substances, processes, or aspects of a living organism that can be used to assess function. In health, biomarkers help doctors monitor for and track disease.
Your blood sugar level, for example, is a biomarker used in the assessment and management of diabetes.
Biomarkers play various roles in CRC. They’re used to evaluate cancer after a diagnosis.
When doctors refer to “biomarker testing” in CRC, they’re typically referring to tumor testing or tumor profiling, which uses a sample of your blood or CRC tissue to study cancer cells and their function.
Biomarker testing in CRC can help distinguish somatic (acquired) genetic mutations from germline (inherited) ones, and can track unusual protein levels, antigens, or abnormalities in cell signaling pathways. It also evaluates the features of cancer that may influence its progression or treatment, like its size and location in the large intestine.
CRC can test positive for one or multiple biomarkers.
Some common biomarkers in CRC include:
- MSI-H/dMMR: Looks at microsatellites (MS), short sections of repetitive DNA, and the function of DNA mismatch repair (MMR) genes, which could be referred to as MSI-H (microsatellite instablity-high) or dMMR (deficient mismatch repair).
- Sidedness: Indicates which side of the intestine CRC is found.
- KRAS: Screens for mutations in the KRAS gene, which is responsible for producing KRAS protein.
- CEA: Measures levels of carcinoembryonic antigen made by cells in the gastrointestinal system.
- ctDNA: Measures small fragments of circulating tumor DNA in the bloodstream.
- BRAF V600E: The most common mutation of the BRAF gene in colorectal cancer. Mutations in the BRAF gene can result in uncontrolled cell growth and division, leading to cancer.
- HER2 amplification: If a tumor is positive for HER2, that means there are higher than usual levels of the HER2 protein. If there are too many HER2 receptors on tumor cells, that can result in too many signals telling the cells to keep growing and dividing, which leads to uncontrolled growth and division.
- NTRK fusions: These proteins usually sit on the surface of nerve cells and help them work properly. Your body carefully controls how much of these proteins are made, but an NTRK gene can “fuse” with an unrelated gene. When this happens, it creates an abnormal protein called a TRK fusion protein, which then appears in places it shouldn’t, causing cells to grow and divide too much. This can lead to cancer.
- DPD deficiency: This test looks at cells (not tumor cells) for mutations or protein levels/activity. It’s important to note that DPD isn’t as common as other biomarker tests, and there are no standardized recommendations. Generally, people only get tested after experiencing severe toxicity during cancer treatment.
Anyone who receives a diagnosis of CRC is a candidate for biomarker testing, but not all biomarker tests are necessary for each person. However, every person who is diagnosed with CRC should have their MSI-H/dMMR tested and CEA checked.
Your doctor determines initial biomarker testing in CRC by reviewing your medical and family history alongside your current CRC diagnosis. Certain biomarker tests are recommended before treatment, depending on the cancer’s stage.
What to ask your doctor
Many people aren’t sure if they’ve had biomarker testing. Doctors don’t always use the word “biomarker” when they talk about testing, or the tests may not have happened yet.
It’s OK to ask your doctor about these tests and whether they’ve performed them. Bringing up biomarker testing early in CRC conversations with your doctor keeps you informed and helps you feel in control of your diagnosis.
Questions to consider include:
- Have I undergone tests for all CRC biomarkers? Why or why not?
- If I haven’t had CRC biomarker testing yet, when should I?
- Do I need to have a blood test, or is a tissue sample necessary?
- Will my biomarker testing include genetic testing for inherited mutations?
- How often will I have to have biomarker testing?
- What are the results of my biomarker tests, and what does that mean for my outlook?
Your doctor considers factors like the stage of CRC and tumor characteristics when planning biomarker testing.
Specific biomarker tests take place before treatment and are determined by the cancer stage. Biomarkers can help inform doctors about which treatments are likely to be the most effective.
By stage, biomarker testing typically includes:
Stage 0 and stage 1
- MSI-H/dMMR
- CEA
- metastatic disease biomarkers if stage 1 cancer is recurrent
Stage 2
- MSI-H/dMMR
- CEA
- possible ctDNA
- metastatic disease biomarkers if stage 2 cancer is recurrent
Stage 3
- MSI-H/dMMR
- CEA
- possible ctDNA
- metastatic disease biomarkers if stage 3 cancer is recurrent
Stage 4/metastatic disease
- MSI-H/dMMR
- CEA
- sidedness
- possible ctDNA
- genetic alterations in KRAS, NRAS, BRAF
- HER2 amplification
- NTRK fusions
Biomarker testing in CRC can be extremely accurate when it comes to detection, with rates as high as
The ability to confirm characteristics of cancer is just one aspect of biomarker accuracy. Biomarker testing also adds accuracy to your treatment plan.
The presence, absence, or change in a biomarker can reveal important details to your doctor about cancer’s growth rate, likelihood of spread, recurrence, and treatment response. These details help your doctor treat CRC with the most effective therapies as soon as possible, which can improve your outcome and outlook.
CRC biomarker testing is the foundation of precision medicine and targeted therapy in CRC. According to a review from 2023, targeted therapies can significantly improve survival rates and cancer outcomes for people, including those with the most advanced forms of CRC.
Biomarkers include a range of biological processes, states, and substances that act as indicators of a living organism’s function. In CRC, biomarkers can help can reveal characteristics of cancer to help treatment planning.
Anyone with a diagnosis of CRC can benefit from biomarker testing, but not all tests are necessary for every person. Talking with your doctor about biomarker testing can help you understand which tests are right for you.