Colorectal cancer tumor markers. Cancer therapy efficacy prediction. 14

Colorectal cancer tumor markers. Cancer therapy efficacy prediction. 14

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Leading expert in colorectal cancer genetics and molecular diagnostics, Dr. C. Richard Boland, MD, explains how the miR-21 microRNA tumor marker revolutionizes colon cancer screening and prognosis. This blood-based biomarker helps identify high-risk patients needing colonoscopy while safely deferring invasive procedures for those with low miR-21 levels, potentially transforming early detection strategies.

miR-21 MicroRNA: A Breakthrough Blood Test for Colorectal Cancer Screening and Prognosis

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What Is miR-21 MicroRNA Tumor Marker?

Dr. C. Richard Boland, MD, describes miR-21 as one of approximately 2,000 microRNAs in the human genome that regulate gene expression. Unlike traditional biomarkers, microRNAs are identified numerically rather than by name, with miR-21 emerging as consistently overexpressed in colorectal cancer tissue samples. Through RNA sequencing techniques, researchers can precisely quantify microRNA levels in both tumor tissue and blood samples.

The breakthrough discovery reveals that cancer cells package miR-21 into exosomes that enter the bloodstream, creating a measurable signature. Dr. Boland's research demonstrates that miR-21 levels decrease after tumor removal, confirming its role as a dynamic indicator of cancer presence and treatment response.

Blood Test Advantages Over Traditional Colon Cancer Screening

The potential for a simple blood test to replace or complement colonoscopy represents a paradigm shift in colorectal cancer detection. Dr. C. Richard Boland, MD, emphasizes that elevated miR-21 levels could identify patients requiring immediate colonoscopy, while normal levels might safely delay invasive procedures for 1-2 years. This approach addresses critical limitations of current screening methods by offering:

  • Elimination of bowel preparation discomfort
  • Reduced risk of procedural complications
  • Lower healthcare costs
  • Increased patient compliance with screening

Prognostic Value in Colorectal Cancer Treatment Monitoring

Beyond screening, miR-21 shows promise as a prognostic tool for evaluating treatment efficacy. Dr. Boland's research demonstrates that microRNA levels correlate with tumor burden, decreasing after successful surgical resection. This real-time monitoring capability could help clinicians:

  • Assess surgical completeness
  • Detect early recurrence
  • Personalize follow-up schedules
  • Evaluate response to chemotherapy

Current Technical Challenges in MicroRNA Testing

Dr. C. Richard Boland, MD, acknowledges several hurdles before widespread clinical implementation. MicroRNAs degrade rapidly at room temperature, requiring immediate analysis after blood collection. Hemolysis presents another complication, as red blood cells contain abundant microRNAs that can distort test results. Additional considerations include:

  • Interference from other conditions (heart failure, non-colorectal cancers)
  • Need for standardized collection protocols
  • Development of multi-marker panels for improved accuracy

Future of Non-Invasive Cancer Screening

The research team envisions a two-stage screening strategy where microRNA blood tests triage patients for colonoscopy. Dr. C. Boland, MD, emphasizes that perfect sensitivity isn't essential - high specificity to confidently rule out cancer would represent a major advancement. Future directions include:

  • Developing fecal-based microRNA tests
  • Creating combination biomarker panels
  • Establishing risk-stratified screening intervals
  • Expanding applications to other cancer types

Key Benefits for Patients Avoiding Unnecessary Colonoscopies

Dr. C. Richard Boland, MD, highlights how miR-21 testing could transform patient experiences. By accurately identifying low-risk individuals, many could avoid the discomfort, expense, and potential complications of unnecessary colonoscopies. The psychological benefit of receiving a "low risk" result could improve screening participation rates, ultimately detecting more cancers at earlier, more treatable stages.

As research continues, this precision medicine approach promises to make colorectal cancer screening more personalized, accessible, and effective for diverse populations worldwide.

Full Transcript

Dr. Anton Titov, MD: Cancer prevention is the best cancer treatment. A new tumor marker helps to diagnose colon cancer. It is called miR-21 microRNA. It can be found in blood and in fecal samples.

Dr. C. Boland, MD: Molecular tumor markers in colorectal cancer form the basis of precision medicine approach to treatment. You have identified a new diagnostic and prognostic marker for colorectal cancer called miR-21. You showed that miR-21 is an independent prognostic factor in colorectal cancer. miR-21 also plays a role in assessment of quality of colon cancer surgical treatment.

Dr. Anton Titov, MD: What is miR-21 tumor marker? How does it help with diagnosis and follow-up of patients with colorectal cancer?

Dr. C. Boland, MD: We have about 2,000 microRNAs in our genome. The microRNAs are called "mi" for "micro" and a capital "R" and then a number. MicroRNAs didn't get names, they got numbers. You can use an RNA sequencing technique and measure all microRNAs at once.

You can take colon cancer tissue, do microRNA sequencing and tell exactly the quantitative expression of each microRNA. There were certain microRNA genetic signatures that came up again and again in colon cancers. miR-21 was one of the very commonly overexpressed microRNAs. We didn't anticipate this initially, but this is what turned out to be the case.

These microRNAs get packaged into exosomes and released into the blood. First we found unique microRNA signatures in colon cancer tissue. Then we found some microRNAs appeared in the blood. MicroRNA is significantly increased in the blood of people with colon cancers.

MicroRNA levels also decrease after primary colon cancer tumor is removed. So it looks like a pretty good tumor marker for colon cancer.

We have a number of technical problems to solve. MicroRNAs degrade pretty quickly in the refrigerator. You have to measure microRNA levels right away. Then there are complications when there is hemolysis.

Red blood cells have a lot of microRNAs. When there is hemolysis, it's hard to interpret the results of microRNA level measurement. Other medical problems, for example, heart failure and other cancers cause elevations of microRNA levels. But we will overcome these problems.

It is just a matter of finding the right combination of microRNAs and overcoming the technical issues. We'd like to find a tumor biomarker in fecal test, but having a biomarker for blood test would be the best.

We can say to patient, "You are safe because you don't have a very high level of microRNAs in blood. Your likelihood of having colon cancer is so low that you can wait another year, or even several years, then you can have another microRNA blood test." Or if microRNA levels are high, maybe you need to have a colonoscopy.

We'd like to find simpler, safer, cheaper ways to screen for colon cancer and separate people into those who might need a more invasive procedure like a colonoscopy, and those who are safe for another year or two years.

Dr. Anton Titov, MD: That's an amazing approach, because it can triage the patients and have a blood test with negative predictive value for cancer detection, those who will benefit from a colonoscopy, and those who can wait longer.

Dr. C. Boland, MD: What we really hope for is to find a blood test which says, "You don't need a colonoscopy." It's better, of course, if we can say that a positive test will tell you that you may have a tumor. But I'm not so worried if such microRNA blood test for cancer is not perfectly sensitive.

What we'd like to have is a cancer screening test with high specificity. So that we could reassure person that they don't need to have expensive, invasive, uncomfortable, and potentially dangerous test for colonoscopy. That's what we'd like to do.