DNA and RNA biomarkers

Precision Medicine - Biomarkers & Diagnostics

Investigate DNA and RNA to identify relevant biomarkers

DNA and RNAs are the basis of the constitution of each cell, each organ and therefore each organism.
Isolating these molecules and deciphering their mechanisms makes it possible to identify certain biological markers that will be associated with pathologies or the organism’s response to external agents (drugs, pollution, etc.).

DNA and RNA: Definition and roles

DNA and RNA (deoxyribonucleic acid and ribonucleic acid, respectively) are molecules with differences in their structure and function in the cell.

DNA represents the matrix of all the cells of an organism and contains the encryption of genes. These genes are expressed in the form of RNA: RNA coding for a protein (~2% of the human genome) and non-coding RNA (~20% of the human genome). These genes allow the synthesis of the elementary building blocks of life, promote certain enzymatic reactions and allow an extremely complex regulation of all these elements.
Unlike DNA, which is constituted at birth and changes little over the course of our lives, RNA is constantly evolving, reflecting the general state of health of the cell, organ and organism to which it belongs.

“Knowing our genes, or relevant ones, helps us take charge of our health. If DNA are our blueprints, RNA are the things that help implement the plan. RNA are more changeable and not as stable as DNA”, explain Dr. Sharad Paul, a New Zealand cancer surgeon and author of « The Genetics of Health », a study on the role genes play in life.

Investigate DNA and RNA to identify relevant biomarkers

In the course of researches, the purpose of DNA analysis is to identify genomic mutations (called nucleotide polymorphisms or SNPs). Two main types of mutations are observed:

  • Constitutional genetic alterations, present from birth in all cells of the body and transmissible to descendants. These alterations may be part of the "positive" evolution of a species over time,
  • Somatic genetic alterations, which occur at a very low frequency but which can lead to the development of a pathology (genetic diseases, cancers, etc.).

Some researches are also interested in the analysis of so-called “InDels” sequences, which represent unique sequences that can be inserted or deleted randomly or targeted into the genome of an individual (healthy or sick) or an ethnic group. These processes also represent mechanisms that can lead to the occurrence of a biological phenomenon or disease such as resistance or susceptibility to some infection.

DNA can also undergo “chemical” changes such as the methylation (or demethylation) of a deoxyribonucleic acid. These modifications, sometimes controlled by the cell itself or sometimes undergone by an external agent (pollution, etc.) of the DNA, lead to a change in the expression of genes and induced proteins.

From DNA to RNA

In the process of gene expression (transcription), the genes encoded on the DNA are copied and transcribed into a molecule: RNA. This copy of the gene gives rise to a very large number of RNAs. The best known is the messenger RNA (mRNA). It is intended for the production of proteins, hormones, enzymes, etc.
There is also a very large class of non-coding RNA molecules such as short (microRNA; miRNA), or long (Long non-coding RNA; lncRNA) RNAs. These RNAs are not translated into proteins but have the ability to physically interfere with another RNA, DNA or a protein in order to modify their activities.

In the course of researches, the analysis of certain RNAs aims to identify molecular processes that are naturally controlled by the cell, but which are disrupted in some cases: 

  • Alternative splicing: process allowing one gene to produce several different RNAs (transcripts), and thus several different proteins;
  • Post-transcriptional modifications of RNAs (RNA editing): process allowing to introduce structural modifications of the RNA (polymorphism, methylation...) at the time of its maturation and, consequently, to modify the produced protein;
  • RNA degradation (degradome): process allowing to control the lifespan, and therefore the activity of an RNA molecule, which can be from a few seconds to several days.

DNA and RNA biomarkers in medical practice and clinical trials

DNA and RNA are today used as biomarkers for the diagnosis and prognosis of various diseases. Detectable in tissues or fluids (liquid biopsies: saliva, urine, serum or blood), these nucleic acids are thus considered as routine biomarkers for cancer diagnosis, monitoring of tumor progression and prediction of therapeutic response such as response or resistance to a molecule.

Over the past few decades, clinical trials involving biomarker stratification of patients have proven successful in the development of new drugs. Since the end of 2018, more than 30 drugs have been developed in combination with diagnostic tests to identify the patients most likely to benefit from these new treatments. This approach is followed today for scientists & industrials involved in precision medicine.

RNA Biomarkers: a therapeutic approach in real time

RNA analysis (or gene expression analysis) is a particularly relevant approach in diagnosis and predictive diagnosis with very good experimental results obtained in different diseases, especially in oncology. RNA analysis presents the advantage that it can be performed on a liquid biopsy, especially a blood sample, a non-invasive approach adapted for routine clinical use: ease to use, safe to use, high throughput and low cost.

Compared to analyses carried out on the tumor (random sampling not representative of the diversity of the clonal population) or cerebrospinal fluid in neurodegenerative pathologies (risks for the patient, high cost, low throughput…) or in medical imaging (low throughput, high cost…), the analysis of gene expression on (total) blood fully meets the needs identified by many scientists and medical teams.

RNA biomarkers allow:

  • a very early analysis of the appearance or evolution of the disease,
  • a differential analysis,
  • an informative and accurate analysis,
  • a specific analysis of the response to drug.

In recent years, numerous studies have demonstrated the relevance of using RNA analysis technologies for the identification of relevant diagnostic biomarkers. These RNA detection technologies are today in vitro diagnostic tests (IVD) and allow detection, stratification or therapeutic orientation in patients suffered from breast or colon cancer.