Early cancer detection diagnostic companies have received a lot of attention and venture capital investment over the last few years with numerous labs launching diagnostic tests to address this potentially massive market. While the realized clinical value of these tests for patients is still some way off, many companies have started enrollment in clinical studies and are building databases to advance this technology.
Most of these companies have focused almost exclusively on DNA methylation techniques to identify early signs of cancer. At first glance this makes sense as DNA is now a widely accepted diagnostic method for identify biological changes associated with tumor growth. However, it is perhaps an incomplete approach as the value of RNA testing and its capabilities are rapidly growing. Gene expression, which is an RNA based technique, may prove to be a more powerful tool for the purpose of early cancer detection and screening.
Gene expression and DNA methylation are two distinct molecular processes, with gene expression being the result of methylation. Whatever abnormalities that are found in DNA methylation should also be found in gene expression along with potentially even more clinically relevant information.
Here are the key differences and considerations for each:
DNA methylation is an epigenetic modification involving the addition of methyl groups to DNA molecules, typically at cytosine residues. Aberrant DNA methylation patterns are commonly associated with cancer.
Pros of DNA Methylation for Early Cancer Detection:
Stability: DNA methylation patterns tend to be relatively stable over time and can be detected in easily accessible samples like blood or urine.
Epigenetic Insights: DNA methylation changes can reveal alterations in gene regulation and potential driver events in cancer development.
Wide Applicability: DNA methylation can be used to detect various types of cancer and may have broader clinical utility.
Cons of DNA Methylation for Early Cancer Detection:
Limited Functional Information: DNA methylation alone does not provide direct information about the functional consequences of gene regulation changes.
Heterogeneity: Methylation patterns can vary among different cancer subtypes and individuals, making interpretation complex.
False Positives: Methylation changes may occur in response to factors other than cancer, leading to potential false positives.
When to Use DNA Methylation:
DNA methylation analysis is valuable for non-invasive or minimally invasive early cancer detection, especially when you need stability and broad applicability. It is often used in screening and diagnostic tests, such as liquid biopsies.
Gene expression refers to the process by which information in a gene’s DNA sequence is used to produce a functional product, typically a protein. In the context of cancer detection, gene expression profiling involves measuring the levels of gene transcripts (messenger RNA or mRNA) in a cell or tissue sample.
Pros of Gene Expression for Early Cancer Detection:
Functional Insight: Gene expression analysis provides information about which genes are actively involved in cellular processes, potentially identifying the specific pathways dysregulated in cancer.
Dynamic Information: Gene expression levels can change rapidly in response to physiological conditions or disease, making it suitable for monitoring disease progression and treatment response.
High Sensitivity: It can detect subtle changes in gene expression that may be indicative of early cancer stages.
Cons of Gene Expression for Early Cancer Detection:
Complexity: Analyzing gene expression data has historically been technically challenging and expensive.
Fragility: RNA tends to degrade faster than DNA and is more complex to work with
Limited Causative Insight: While gene expression can reveal dysregulated pathways, it doesn’t directly provide information about the underlying genetic mutations or epigenetic changes driving cancer.
When to Use Gene Expression:
Gene expression profiling is most useful when you want to gain insight into the functional changes occurring in cancer cells and when you need high sensitivity to detect early-stage cancers. It is often employed in research settings and, in some cases, for personalized treatment decisions.
In closing, the choice between gene expression and DNA methylation for early cancer detection is still not clearly defined as to what will be a superior approach. Gene expression provides functional insight and high sensitivity, while DNA methylation offers stability and broader applicability. In some cases, a combination of both approaches may provide a more comprehensive understanding of cancer development and progression.
GTC is currently collecting gene expression data as RNA in our opinion has several distinct advantages over DNA-only approaches. Learn more about GTC’s Gene Expression capabilities for research.
Time and billions of dollars will ultimately tell which of these applications are more clinically useful. We even must leave open a possibility that another approach may make sense to early cancer detection and screening. But for now, we will have to wait for more data to be collected and outcomes to be analyzed.