Ask BioChain: The Role of Biomarkers in Clinical Research

When asked to diagnose an illness, the first thing medical professionals usually look at are the symptoms. Some symptoms are unique to one disease; others could mean many things. Either way, the symptom indicates a greater truth about whichever condition is being discussed.

Reliable, robust indicators are important no matter what you’re studying, but especially so in clinical research. Sometimes, the best indicators available for ethical, pragmatic conduct of a clinical trial are biological markers.

Known as biomarkers, these are characteristics of biological tissue, or biospecimens, that can be studied to determine the function, expression, or behavior of a clinical subject. In biomolecular clinical research, the clinical subject is the biospecimen, and biomarkers are one of the tools that allow researchers to characterize and study that tissue, as well as any condition or illness that might be associated with it.

At BioChain Institute, Inc. our scientists pride themselves on offering our clients a wide range of high-quality biological specimens for use in all kinds of clinical research. The role of biospecimens in clinical research is complex and multi-faceted, so we’ve built this new series of articles to help unpack the many dimensions of biospecimens as they’re used in clinical research. 

Biomarkers are the building blocks of any given tissue sample; let’s start there. 

What Are Biomarkers?

What are biomarkers and why are they useful? 

Biomarkers can be defined as characteristics of whatever biological specimen you are studying. These characteristics act as metrics of evaluation used in clinical, biological, and medical contexts. Biomarkers can be objectively quantified and then evaluated as indicators of normal or pathogenic behavior. Biomarkers can also be used as indicators of reaction (positive, negative, or neutral) on the part of the subject to therapeutic agents or interventions.

All biomarkers come from biospecimens, and all biospecimens have a unique biomolecular makeup that can be broken down into component parts – both cellular and molecular – and analyzed. These components can be analyzed according to genetic makeup, processes that dictate their behavior, or functions they do or do not serve. 

To better understand the range of biomarkers out there, we have to understand that characteristics or features of biospecimens that are measurable can be molecular, histologic, radiographic, or physiological in origin. A biomarker can be something as granular as the gene APOE for detecting colon cancer, or as systemic as high blood sugar for detecting diabetes.

Types of Biomarkers

There’s a lot of overlap in the types and applications of different biomarkers. The complexity of human body systems, especially at the cellular level, means that one small thing could be connected to, and indicative of, a hundred other minor or serious things. 

BioChain’s biospecimens are characterized by their molecular biomarkers, and when discussing biomarkers at the molecular level, this versatility becomes even more apparent. One gene or protein could be reasonably used to measure, detect, and monitor a wide range of diseases, responses to treatments, or predispositions. For example, overexpression of the lipid metabolizing protein APOE can be used in the detection of certain cancers, while its underexpression is associated with the risk of Alzheimer’s. 

Despite this versatility, the FDA classifies biomarkers into 7 categories: risk, diagnostic, monitoring, prognostic, predictive, response, and safety. Most of the biomarkers supplied by BioChain fall into the categories of prognostic and predictive biomarkers.

Prognostic: used to measure the likelihood of a clinical event or outcome and/or recurrence after the diagnosis of a condition or disease. Prognostic biomarkers can also be used to plot a timeline for recovery if the prognosis is positive. An example of a prognostic biomarker is HER2 protein overexpression in breast cancer.  

Predictive: used to determine the likelihood of groups, types, or categories of individuals developing a condition or disease when compared to comparative/counterpart individuals. Mutations to Breast Cancer gene 1 or 2 are used as predictive markers for evaluating whether ovarian cancer patients may respond positively to certain treatments.

Other biomarkers are used to evaluate things such as patients’ likelihood of developing disease, determining the active presence of a condition in a patient, monitoring that condition, and whether or not a patient is reacting to a treatment. 

In addition to these classifications, all biomarkers used in clinical research are also classified as clinical biomarkers by default.

The Role of Biomarkers in Clinical Research

Not all biomarkers can be used in clinical research. To be useful in a clinical trial, biomarkers must be:

  1. Accurately, regularly measurable at a reasonable cost
  2. Ethically accessible
  3. Able to communicate information not clear through clinical assessment (for example, a physical check-up)
  4. Ultimately useful to clinical decision-making

As discussed, one biomarker could be indicative of many different conditions; most of the time, many biomarkers are evaluated alongside each other for robust results. Some very well-established biomarkers, such as total cholesterol, have been accepted by regulatory authorities as reasonable clinical endpoints, or definitive indicators of a condition. Most biomarkers, however, don’t fall into this category and have to be used in conjunction with other metrics to draw reliable clinical conclusions. This is especially true of more granular biomarkers, or biomarkers at the molecular level.

Despite their complexity, biomarkers are incredibly important in successful clinical research. Different intersections or permutations of biomarkers and their varying, unique levels of expression are used in clinical research to understand both normal and diseased physiological and molecular processes. Through this understanding, scientists can understand disease progression and associated treatment, develop drugs, therapeutic technologies, and/or medical devices, and develop standards of clinical practice.   

So where does BioChain come into this? BioChain specializes in genetic or molecular biomarkers. Genetic biomarkers play a crucial role in clinical research across various fields,

including oncology, pharmacogenomics, and rare genetic disorders. BioChain supplies clinical researchers with the characterized biospecimens they use in their research. It’s through these specimens that biomarker expression, interaction, and associated clinical learning can be achieved.


Why Characterize Biospecimens?

Biomarkers range from systemic or organ-based classification, like high blood sugar, to more granular or molecular-based classification, such as a specific protein. In spite of this diversity, the term biomarker is most commonly used to refer to the molecular kind. 

Molecular biomarkers can be either genomic (genes) or proteomic (proteins). Traditionally, a given blood protein level would present a proteomic biomarker, while alterations in the mRNA of a gene would present a genomic one.  

When a tissue’s biomolecular makeup is characterized, a list of all the potential molecular biomarkers in the biospecimen is generated. At BioChain, we offer a large range of characterized diseased, normal, and matched pair tissues for use in clinical research. These biospecimens are characterized for DNA, RNA, and protein; their molecular characteristics, as both existing or novel biomarkers, can be used as controls or references in clinical trials. 


Molecular Biomarkers in Clinical Research

While there are only a few molecular biomarkers that have been formally approved by the FDA for use as biomarkers in clinical research, thousands are still used and evaluated in clinical trials every day.     

BioChain Institute, Inc. is a company that offers high-quality biospecimens for research in molecular oncology, histopathology, and other clinical arenas. As a result, the markers characterized in our biospecimens are exclusively molecular.

At BioChain, we conduct in-house characterization of our biospecimens to generate all the molecular biodata in that specimen, including information on mutation levels, methylation levels, and protein expression; because of the latter, these specimens can be used as controls and references in clinical research.


Genomic Biomarkers

BioChain’s genomic biomarkers can be used in the analysis of clinical subjects’ genetic makeup, capturing genetic variations such as single nucleotide polymorphisms, copy number variations, and general mutations. Genomic biomarkers are used in clinical research to identify genetic predispositions to diseases, predict treatment responses, and guide personalized medicine approaches.


Gene Expression Biomarkers

BioChain carries a variety of high-quality biospecimens characterized according to different gene expression biomarkers, or biomarkers that can be used in clinical research to assess variations in and degrees of genetic expression. For example, BioChain’s CancerSeq line offers tissues specifically sequenced for cancerous hotspot mutations. These specimens, available as paraffin-embedded or fresh frozen samples, are characterized using deep sequencing Next Generation Sequencing (NGS) methods with high coverage. 

BioChain offers various FFPE tissues with the below gene expression biomarkers:

BRCA: BRCA1 and BRCA2 are genes associated with hereditary breast and ovarian cancer syndrome. Mutations in these genes increase the risk of developing breast, ovarian, prostate, and other cancers. Gene expression profiling can help identify abnormal activity in these genes.

EGFR: Epidermal Growth Factor Receptor (EGFR) is a gene commonly associated with several types of cancer, particularly non-small cell lung cancer (NSCLC). EGFR mutations can lead to uncontrolled cell growth and cancer progression; measuring this biomarker’s expression can guide targeted therapy decisions.

MSI: Microsatellite Instability (MSI) is a biomarker associated with DNA mismatch repair deficiency. High levels of MSI are often found in certain types of colorectal cancer. MSI status can help predict the response to immunotherapy drugs called immune checkpoint inhibitors.

KRAS: KRAS is a gene involved in cell-signaling pathways that regulate cell division and growth. Mutations in the KRAS gene are commonly found in several types of cancer, including colorectal cancer, lung cancer, and pancreatic cancer. Treatment options can be tailored according to which KRAS mutation is found.

HPV (Human Papillomavirus): HPV infection can lead to the development of viral oncogenes such as E6 and E7, which promote cell transformation and cancer development. HPV testing and gene expression profiling can help gauge the likelihood of developing cervical cancer and other cancers of the genitals, anus, and oropharynx.


DNA Methylation Biomarkers

The addition of methyl groups to DNA can regulate gene expression in different ways. Aberrant DNA methylation patterns are associated with cancer, autoimmune diseases, and other conditions. BioChain’s methylated DNA can be used for early detection of cancer, risk assessment, and monitoring treatment response.


Epigenetic Biomarkers

BioChain offers cell-free DNA, cell-free plasma, and mutation quantification in plasma, all of which are valuable for evaluating biomarkers in epigenetic research. These tools offer non-invasive methods for studying epigenetic modifications and genetic alterations associated with various diseases. Integrating these approaches to biomarker evaluation can provide a holistic understanding of the molecular mechanisms underlying disease development and progression, ultimately leading to improved diagnostics and therapeutic interventions.


Protein Biomarkers

BioChain’s high-quality protein samples can be used as reference materials to measure levels of specific proteins in bodily fluids like blood, urine, or cerebrospinal fluid. They can indicate disease presence, progression, or response to therapy.


Spatially Characterized Tissues

Finally, BioChain offers uniquely characterized biospecimens in the form of spatially characterized tissues. We characterize our tissues using 10x Visium and NanoString GeoMx technologies capable of capturing both the biomarkers present in a given tissue sample, as well as their spatial context and distribution relative to the rest of the tissue!

The role of biomarkers in clinical research is wide and varied. From confirming a known disease through widely accepted marker expression to discovering novel genomic interactions, biomarkers’ necessity for clinical research cannot be clearer. In turn, the availability of high-quality biospecimens through which to access these markers is invaluable to clinical scientists working at all levels of the research process.


If you’re interested in using BioChain’s biospecimen samples and associated biomarkers for your clinical research, please contact us.