What Are Colorectal Cancer Biomarkers?

Biomarkers, also known as biological markers or molecular markers, are small molecules that cancer cells produce. These substances can be proteins or even DNA mutations in a cancer cell. And they can be found in your blood, body fluids, or in the tumor itself.

If you or a loved one has been diagnosed with colorectal cancer, you may be familiar with biomarkers. But sometimes it can be difficult to understand how they can affect the care and management of your specific cancer. Care teams can use different biomarkers in colorectal cancer to personalize treatment, estimate prognosis, or even identify cancer recurrence. We’ll discuss the most commonly checked biomarkers in colorectal cancer, and the role they play in your cancer treatment plan.

What is the main colorectal cancer biomarker? 

The protein carcinoembryonic antigen, or CEA, is the most recognized biomarker for colon cancer. It was the first colon cancer biomarker discovered — back in 1965. And up to 90% of colorectal tumors produce it. 

But researchers have since learned that CEA isn’t necessarily the most useful biomarker. There are several reasons for this: 

• It isn’t specific to colorectal cancer. It can also be elevated in other types of cancers, like pancreatic, ovarian, thyroid, breast, gastric, and lung cancers. 

• CEA can even be elevated in noncancerous conditions. 

• The test can be normal even when there is an active cancer, so it’s less ideal for screening.

So CEA is no longer considered a useful marker to diagnose colorectal cancer. But it’s still used for monitoring disease progression once colorectal cancer is diagnosed. More on this below.

What other colorectal cancer biomarkers are there?

Researchers are currently studying several biomarkers that can help personalize the treatment for specific colorectal cancers. These biomarkers provide information about how a certain tumor will grow and behave. And this information helps determine how to best fight the cancer cells. A few biomarkers that providers commonly check include:

• Microsatellite instability (MSI): Microsatellites are repeating sequences of DNA in our genes. Sometimes these sequences are copied incorrectly when our cells divide, causing the DNA strands to become unstable. This is called “microsatellite instability,” and it occurs in approximately 20% of stage 1 and 2 colon cancers. It’s less common in higher stages. 

• KRAS, NRAS, and BRAF: These are genes found in every cell in our body, and they help our cells know when to grow and divide. Usually they can be turned on and off as needed for normal cell growth. But sometimes these genes develop mutations. When these mutations occur, normal cells can become cancerous and grow uncontrollably. KRAS mutations happen in about 45% of colorectal cancers, NRAS mutations are found in approximately 3% of colon cancers, and BRAF mutations occur in about 13% of colorectal cancers. 

• Human epidermal growth factor receptor 2 (HER2): HER2 is a protein that’s present in normal cells. But colorectal cancer cells can have too much of this protein in approximately 3% of cases. This leads to uncontrolled cell growth. HER2 is also checked as a biomarker in other types of cancer, including breast and gastric cancers. 

These biomarkers are usually measured in the tumor cells from a biopsy sample. Sometimes they can be measured by a blood test, like CEA, but this is less common.

How are colorectal cancer biomarkers used?

Different biomarkers can provide different types of information. Your care team can then use that information to predict the behavior of your particular cancer. The information biomarkers can show includes: 

• Response to treatment: If CEA is initially elevated, it should decrease during and after cancer treatment when that treatment is successful. 

• Cancer recurrence: CEA can also be used to monitor for possible cancer recurrence after treatment is completed. 

• Prognosis: Colorectal cancers that have high microsatellite instability often have better prognosis in earlier stage disease (stage 1 or 2). And they may respond to immunotherapy in metastatic (stage 4) disease. 

• Risk factors for other cancers: If your cancer has high microsatellite instability, your healthcare provider may check for a genetic condition called Lynch syndrome, also called “hereditary non-polyposis colorectal cancer” (HNPCC). This condition predisposes people to certain cancers — like colorectal cancer and cancer of the uterine lining (endometrium). In addition to more frequent colonoscopies, individuals with colon cancer who are diagnosed with Lynch syndrome may also need more frequent screening for other types of cancers. 

• Targeted therapies: Certain biomarkers, when present, can indicate which treatments will be most effective. KRAS, NRAS, and BRAF biomarkers are all used to figure out which treatments will work the best. And colorectal cancers that have high amounts of HER2 can be treated with therapies that specifically target this receptor. 

When are colorectal cancer biomarkers tested?

Biomarkers are checked at different times — and in different people — depending on the circumstances.

CEA is checked in most people at the time of diagnosis. It’s then routinely checked during treatment to make sure the treatment is working. And then it’s checked after treatment is complete to monitor for recurrence (surveillance) for up to 5 years.

Microsatellite instability is usually tested in all people at the time of diagnosis to help determine prognosis and which treatments may work best.

KRAS, NRAS, BRAF, and HER2 are tested in people who have metastatic colorectal cancer — or colorectal cancer that has spread to other organs. 

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Written by:

Joanna Jan, MD

Joanna Jan, MD, is board-certified in internal medicine and licensed to practice medicine in the state of Pennsylvania. In 2017, she received her board certification from the American Board of Internal Medicine.

Edited by:

Katie E. Golden, MD

Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.

Reviewed by:

John Strickler, MD

John Strickler, MD, joined the Duke University faculty in 2011 and is now an associate professor of medicine in the division of medical oncology. His research focuses on precision cancer medicine: identification of genomic biomarkers that predict sensitivity or resistance to targeted therapies and immunotherapy.

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