Imagine a world without routine colonoscopies. Because of a new blood test we developed at Baylor Research Institute, this could potentially become a reality.
Our team of researchers at the Gastrointestinal Cancer Research Lab has spent the last several years working on the discovery and validation of biomarkers that can facilitate the early detection of colorectal polyps and cancers.
This test measures the level of a microRNA—a small RNA molecule that can be identified in a blood test. To do this, we looked at several hundreds of patients with colorectal polyps and cancers. We found that by measuring levels of a single microRNA (called miR-21) in the blood, we could identify 92 percent of patients with colorectal cancer.
In addition, we discovered that we could identify 82 percent of patients with advanced colonic polyps that are at risk for developing into colorectal cancers over the next few years. The concept is that those individuals with a positive test would then have the lesion removed by colonoscopy.
Those with a low risk of harboring a dangerous lesion in their colons could wait for some period of time before having another test, postponing the need for a screening colonoscopy, most of which detect no lesions.
We would like to distinguish asymptomatic individuals, who are likely to benefit from a therapeutic colonoscopy, from those who actually have nothing in their colons and don’t need the test.
The key to this study was examining the expression of circulating microRNAs. Our body has about 22,000 protein-encoding genes but a large variety of other RNA molecules that are involved in the regulation of gene expression without encoding a protein.
One type of non-coding RNA is the microRNAs, which are very small genes involved in controlling the expression of other genes by regulating the stability of protein-encoding genes, including some that are involved in carcinogenesis.
Over the past decade or more, a lot of effort has been spent in developing gene-based biomarkers, which has met with limited success because most human genes are relatively large and are vulnerable to degradation, making it challenging to measure their expression in tissues and bodily fluids with confidence.
What makes microRNAs unique is that they are small and resistant to degradation. Thus, their expression can be accurately measured in a wide variety of tissues, body fluids and even archival clinical specimens. Because of their small size, microRNAs are easier to analyze than most protein-encoding genes.
With this blood test, we can measure the level of microRNAs in the blood—find the patients with early cancers and advanced polyps and remove them while they are almost always curable. That’s great news for the patient—to have these clinically dangerous polyps taken out, knowing that once removed, the polyp cannot continue to grow (silently) and develop into a cancer.
As a researcher and doctor, the most exciting part about the test is that it provides the potential for development as a non-invasive blood test that can be routinely used for colon cancer screening and may help identify individuals with early stage, silent tumors in the colon and rectum.
At present, the only tests available are those that test for blood or DNA in the stool, or direct visualization of the colon with a scope, X-ray, or other invasive technology. Many people will simply refuse invasive tests or those that involve stool. It is widely believed that most people would agree to a blood test to screen for colorectal cancer risk – if an effective test were available.
What inspires us to keep working on this research is that colon cancer is the third most common cancer and the second leading cause of cancer-related deaths in the U.S. There are about 150,000 new cases diagnosed with colon cancer yearly, and about 50,000 people die of this each year.
Colon cancer is realistically a preventable disease if identified early. Detection of an advanced adenoma or a stage I cancer is almost always curable. However, part of the reason people die from colon cancer is that we don’t detect it early enough.
Colorectal cancer is a silent disease early in its course, and there are few warning signs. A substantial proportion of people are diagnosed with the disease during a diagnostic colonoscopy performed for symptoms, when the disease is likely to be advanced, requiring surgery and chemotherapy and there’s a risk of death.
We do not wish to overstate the conclusions of this study at this point. Research moves ahead step by step, and it will take confirmation of this in another study and refinement of the sensitivity and specificity of this approach.
This round of work is being published in the Journal of the National Cancer Institute, where other research groups will read, react and perhaps try to confirm our findings.
If this work stands the test of time, and we make the test more accurate, it could potentially transform clinical care. However, we still have a long way to go.
We will now go through another level of validation in several hundreds or thousands of patients. We are currently seeking partners such as major pharmaceutical companies or other health care organizations that may be interested in this work to collaborate with this research.
There is a clear need to develop non-invasive tests for colorectal cancer screening. Colonoscopic surveillance is the best approach we have at this time, but this technology is invasive and expensive, and many people at risk for colorectal cancer will either refuse it, or not be able to afford it.
Current screening guidelines for colon cancer recommend screening every 10 years starting at age 50.
If there were a blood test with a sensitivity as good as, or nearly as good as, colonoscopy, it could be used to determine which people would be most likely to benefit from therapeutic colonoscopy and spare those at low risk from a procedure that they do not need. The goal is to protect patients from a deadly disease in the safest and most cost-efficient manner.
Everyone wants non-invasive and less-expensive tools to screen for all types of cancer. This work is a step forward in that direction.
This article was contributed by Ajay Goel, PhD.