MicroRNA Biomarkers: A Breakthrough in Non-Invasive Colon Cancer Screening

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• MicroRNA in Colon Cancer Detection
• Limitations of Current Colon Cancer Screening Methods
• Fecal vs Blood Tests for MicroRNA Detection
• Advantages of MicroRNA Analysis Over DNA Testing
• Detecting Precancerous Lesions Before Cancer Develops
• Future Directions in Colon Cancer Screening
• Full Transcript

MicroRNA in Colon Cancer Detection

Dr. C. Richard Boland, MD reveals how microRNAs - small genetic molecules found in colon cancer tumors - can be detected in both blood and fecal samples. These biomarkers offer a revolutionary approach to non-invasive colon cancer screening. The discovery that microRNAs remain stable in fecal samples surprised researchers, as these molecules were initially thought to be too fragile for detection in stool.

Several companies in the US and Europe are now developing commercial tests that analyze microRNA patterns for early colon cancer detection. Dr. C. Boland, MD, emphasizes that these genetic signatures appear not just in malignant tumors but also in advanced precancerous adenomas, making them ideal for preventive screening.

Limitations of Current Colon Cancer Screening Methods

Traditional colon cancer screening methods face significant challenges, as explained by Dr. C. Richard Boland, MD. The guaiac fecal occult blood test and newer fecal immunochemical tests (FIT) have sensitivity and specificity limitations. These blood-based stool tests can produce false positives from non-cancerous bleeding sources like hemorrhoids or gum disease.

Dr. C. Boland, MD, notes that current approaches requiring patients to collect and mail stool samples face compliance challenges. Many people find the process unpleasant, leading to lower screening participation rates despite colon cancer being one of the most preventable cancers when caught early.

Fecal vs Blood Tests for MicroRNA Detection

While fecal microRNA analysis shows promise, Dr. C. Richard Boland, MD suggests blood-based testing might ultimately prove more acceptable to patients. Blood tests eliminate the compliance barriers associated with stool collection while potentially offering similar detection capabilities.

However, for patients willing to provide fecal samples, Dr. Boland strongly advocates including microRNA analysis in any stool-based screening. He explains that microRNAs provide a stronger biological signal than DNA mutations because each cell contains multiple copies of these molecules compared to just two DNA copies.

Advantages of MicroRNA Analysis Over DNA Testing

Dr. C. Richard Boland, MD highlights key technical advantages of microRNA biomarkers compared to DNA-based testing approaches. Some companies are attempting to combine fecal immunochemical tests with analysis of methylated DNA and KRAS mutations, but Dr. Boland considers this approach unnecessarily complex.

"MicroRNAs should be very easy to measure," explains Dr. Boland. The natural amplification of microRNA signals in cells makes them particularly sensitive markers for early cancer detection. This amplification effect could allow identification of tumors at earlier stages than current methods permit.

Detecting Precancerous Lesions Before Cancer Develops

A critical advantage of microRNA screening, according to Dr. C. Richard Boland, MD, is its ability to identify precancerous adenomas before they become malignant. Current fecal blood tests often only detect cancer after it has progressed to bleeding stages, missing the optimal window for prevention.

"Colon polyp doesn't have to be fully malignant to get these abnormal microRNA genetic signatures," notes Dr. Boland. This capability could transform colon cancer screening from early detection to true prevention by enabling removal of dangerous polyps before cancer develops.

Future Directions in Colon Cancer Screening

Dr. C. Richard Boland, MD envisions a future where microRNA analysis becomes standard in colon cancer screening programs. He emphasizes the need for tests that are both highly sensitive and specific to colorectal abnormalities, reducing false positives from other gastrointestinal sources.

As research progresses, combining microRNA signatures with other biomarkers may further improve screening accuracy. Dr. Boland's work suggests that within several years, patients may have access to simple blood tests that provide colon cancer risk assessment comparable to current stool-based methods but with greater convenience and patient acceptance.

Full Transcript

Dr. Anton Titov, MD: Colon cancer screening by non-invasive methods is important. New sensitive colon cancer tumor markers are found. Identification of microRNA in fecal samples and in blood can predict cancer risk.

Colorectal cancer is the most common cancer when considering women and men together. Almost 1.5 million people around the world are diagnosed with colon cancer each year. Yet colon cancer deaths can be entirely preventable through screening for precancerous polyps and early detection of colon cancer tumors.

Colonoscopy remains the standard method of screening for colon cancer, but less invasive methods are being developed. MicroRNA identification is a non-invasive colon cancer screening method. You have shown that microRNA can be identified in fecal samples. So microRNA from colon cancer tumors can serve as a biomarker for early detection of colorectal cancer by analyzing a small fecal sample.

Dr. Anton Titov, MD: How can microRNAs be used in colorectal cancer screening?

Dr. C. Boland, MD: We have just discussed finding miR-21 and other microRNAs in the blood. Several years ago, one of the research fellows in the lab suggested that microRNAs differentially expressed in colon cancer might be present in stool. Initially, I didn't think we could find microRNAs in fecal samples. I thought microRNAs would be too fragile and broken down in feces. But it turned out he was correct—we can isolate microRNAs in fecal samples.

There is at least one company in the USA and more in Europe working on methods of early colon cancer detection by analyzing fecal samples. Identification of microRNAs is one way to find early colon cancer.

So far, we have used a guaiac test to detect blood in fecal samples for early colon cancer detection. Now most people use a fecal immunochemical test, but it still has sensitivity and specificity problems for cancer detection.

One company in the United States is adding methylated DNA analysis and KRAS tumor mutation analysis to fecal testing for colon cancer. I think it's too hard to do that—it will be very difficult to make such fecal sample tests work well. MicroRNAs should be very easy to measure. I'm hoping they will start incorporating microRNA analysis in fecal sample testing for colon cancer.

The problem is that many people find it difficult to collect a stool sample, put it in the mail, or give it to their doctor. People just don't like to do that. So a blood test would be better. But if people are going to do any kind of fecal test to detect colon cancer, they must test for microRNAs.

There are multiple copies of microRNAs in each cell but only two copies of DNA. So with microRNAs, you have an amplified signal by definition. Companies working on early colon cancer detection methods must look at microRNAs. If you're going to measure anything in stool, microRNAs will probably be the most sensitive test for finding early-stage colon cancer tumors.

Dr. C. Boland, MD: These microRNAs are present in colon cancer tumors but also in advanced colon adenomas. A colon polyp doesn't have to be fully malignant to have these abnormal microRNA genetic signatures. This will be a very exciting non-invasive early screening method. It's important to identify precancerous lesions because finding blood in feces signifies that colorectal cancer has already become quite advanced.

Yes, another problem with blood in feces is that it can come from anywhere in the gut. You could have bleeding from your gums or hemorrhoids. If we can find a test for early colon cancer detection that is very specific for cancer identification, it will be much more powerful.