TYPES OF BIOMARKERS

Mandeep SinghB.Sc. (H) Medical Biotechnology

Types Of Biomarkers There are mainly four types of molecular biomarkers :Genomic biomarkers: based on the analysis of DNA

(deoxyribonucleic acid) profiles, especially the analysis of SNPs (single nucleotide polymorphisms), i.e. identification of punctual variations in genomic DNA.

Transcriptomic biomarkers: based on the analysis of RNA expression profiles.

Proteomic or Protein biomarkers: based on the analysis of the protein profiles.

Metabolomic biomarkers: based on the analysis of metabolites (metabolites are the inter-mediates and products of metabolism).

Genomic Or DNA BiomarkersA measurable DNA characteristic that is an indicator of

normal biologic processes, pathogenic processes, and/or response to therapeutic or other interventions.

Scientists have discovered that virtually all cancers carry somatic DNA mutations. Unlike hereditary mutations that are passed from parent to child and are present in every cell in the body, somatic mutations form in the DNA of individual cells during a person's life. Because these somatic mutations are only present in tumor cell DNA, they provide an extremely specific biomarker that can be detected and tracked.

Mutations in oncogenes, tumour-suppressor genes, and mismatch-repair genes can serve as DNA biomarkers.

Genomic Biomarkers

In a new study published in Science Translational Medicine Journal scientists have discovered that dying tumor cells release small pieces of their DNA into the bloodstream. These pieces are called cell-free circulating tumor DNA (ctDNA). This study examines the potential of screening ctDNA for somatic mutations as a way to detect and follow the progression of a patient's tumor.

Mutations in other cancer-related genes, such as the RAS oncogene or the tumour-suppressor genes CDKN2A (cyclin dependent kinase inhibitor A, which encodes p16INK4A), APC (the adenomatous polyposis coli gene) and RB1 (the retinoblastoma gene), also have the potential as markers for prognosis or selection of therapy.

Genomic biomarkers in cancer Drug discovery

Transcriptomic BiomarkersThe transcriptome is the set of all RNA molecules,

including mRNA, rRNA, tRNA, and other non-coding RNA produced in one or a population of cells. It differs from the exome in that it includes only those RNA molecules found in a specified cell population, and usually includes the amount or concentration of each RNA molecule in addition to the molecular identities.

RNA-based biomarkers undergoing clinical evaluation consist of multi-gene molecular patterns or ‘fingerprints’.

For example, pattern-based RNA expression analysis of clinical breast cancers has identified previously unknown molecular subtypes that are associated with differences in survival.

Transcriptomic BiomarkersThat analysis has also provided increased prognostic

capability, predicted response to neo-adjuvant therapy, predicted the likelihood of metastasis in lymph-node negative patients and correctly predicted tumour grade

from laser-capture microdissected specimens.Gene expression profiling offers an unparalleled

opportunity to develop biomarkers that are useful in diagnosis and prognosis and in helping to achieve the goal of individualized cancer treatment.

Transcriptomic biomarkers use in Cancer drug discovery

Proteomic BiomarkersProteomics is the large-scale study of proteins,

particularly their structures and functions.Proteomics technologies are emerging as a useful

tool in the discovery of cancer biomarkers.These advances overcome in part the complexity

and heterogeneity of the human proteome, permitting the quantitative analysis and identification of protein changes associated with tumor development. With the advent of new and improved proteomic technologies, it is possible to discover new biomarkers for the early detection and treatment of cancer.

Ongoing & anticipated implications of Proteomics biomarkers in medicine

Proteomic-based approaches for biomarker investigation can be employed in different aspects of medicine, such as –

1. elucidation of pathways affected in disease,

2. identification of individuals who are at a high risk of developing,

3. identification of individuals who are most likely to respond to specific therapeutic interventions, and prediction of which patients will develop specific side effects

Proteomics biomarkers use an effective Dignostic Biomarker

Metabolomic BiomarkersMetabolomics is the "systematic study of the unique chemical

fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles.

Metabonomics, was introduced to refer specifically to the analysis of metabolic responses to drugs or diseases. Metabonomics has become a major area of research; it is the complex system biological study, used as a method to identify the biomarker for various disease.

In general, in most disease cases, a metabolic pathway had or has been either activated or deactivated - this parameter can thus be used as a marker for some diseases.

For eg., Serotonin production pathways, activated in a person who has recently consumed alcohol for instance, can be a metabolic marker of recent alcohol consumption.

Metabolomic BiomarkersThe feasibility of metabolomics for biomarker

discovery is supported by the assumption that metabolites are important players in biological systems and that diseases cause disruption of biochemical pathways. In fact, metabolomics, has shown to have benefits in various clinical areas.

Compared to classical diagnostic approaches and conventional clinical biomarkers, metabolomics offers potential advantages in sensitivity and specificity.

Despite its potential, metabolomics still retains several intrinsic limitations which have a great impact on its widespread implementation. 

Metabolomic approach in Cancer dignosis

Types of Biomarkers Based upon application and Use in Drug Development and Disease Management