Earlier in this series, we defined and described biomarkers: characteristics of biological tissue that can be studied to determine the function, expression, or behavior of a clinical subject. Biomarkers can be quantified and measured as characteristics of either normal or pathological behavior. They’re used in the molecular research of a whole range of diseases – the most significant of which might be cancer.
BioChain works predominantly with genomic or molecular biomarkers. Our high-quality biospecimens are characterized in-house for a wide diversity of markers. Highly versatile, one single genomic biomarker can be used to study a wide range of different diseases, responses to treatments, or patient predispositions. Knowing the significance of high quality biomarkers to the progress of cancer research, we wanted to use the latest addition to this blog post series as an opportunity to explore that role, and the unique features of our cancer-specific products.
Cancer and Biomarkers in Molecular Research
Cancer is a condition that claims the life of hundreds of thousands of Americans every year. Because it can be such a systemic disease, many biological markers are associated with it. Even with our genomic focus, the range of genes and proteins whose expression can be measured to better understand the expression and treatment of the diseases is vast.
This versatility is not a negative, however. The significance of high quality biomarkers in the progress of cancer research cannot be overstated. By studying genomic biomarkers, we are capable of determining the unique patterns of mutation that characterize particular carcinomas, adenomas, and that generally drive tumor growth. A revolutionary development in the study of cancer diagnostics and treatment, biomarker testing has become invaluable to developing and prescribing targeted cancer therapies. Biomarker testing can be used for preventative, diagnostic, and prognostic approaches; used correctly, it can assess individuals’ risk of developing cancer in the future or risk of cancer recurrence, predict the efficacy of a therapy or treatment, and monitor the progress of that treatment.
Common Categories of Cancer Biomarkers
Cancer biomarkers can be organized and understood based on function (e.g. diagnostic, prognostic, or predictive), patterns of regulation and expression (e.g. transcription factors), and molecular type (e.g. nucleic vs protein).
Prognostic and Predictive Cancer Biomarkers
BioChain specializes in predictive and prognostic biomarkers. Prognostic biomarkers are used to measure the likelihood of a clinical event or outcome and/or recurrence after the diagnosis of a condition or disease. If a cancer prognosis is positive – that is, the patient will survive their cancer – these biomarkers can be used to project a timeline for the patient’s recovery.
Predictive biomarkers are more general; they’re used to determine the likelihood of groups, types, or categories of individuals developing a type of cancer when compared to comparative/counterpart groups.
For example the HER2 protein is a well known prognostic biomarker for the development of breast cancer. Overexpression of this protein is correlated with rapid tumor growth in the breast. Similarly, mutations to Breast Cancer gene 1 or 2 are used as predictive markers for evaluating whether breast cancer patients may respond positively to certain treatments.
Predictive and prognostic biomarkers have played an important role in the growth of precision medicine and the evolution of approaches to cancer treatment. Using known and novel cancer biomarkers, researchers are able to characterize targetable points in cancer cells – biomarkers which, if altered appropriately, can change the course of the cancer’s progression.
Transcription Factors and Cell Surface Receptors
Transcription factors refer to a group of proteins called STATs that regulate gene expression. Often, in cancer cells, these proteins are dis- or abnormally regulated. Their dysregulation can influence tumor growth, metastasis, and treatment resistance, making them vital targets for cancer therapies. STAT proteins are considered a promising target for evolving cancer therapies because they are not vital to normal cell function. Ongoing research aims to unpack and explore the specifics of how this group of cancer biomarkers can be leveraged to develop less toxic oncological treatments.
Like their name suggests, cell surface receptors are molecules like proteins or carbohydrates expressed on the surface of a cell membrane, making them easy to use as biomarkers of specific cell types in cancer research. These markers can be used to classify cells as cancer cells for research purposes. Furthermore, abnormal signaling and expression from these receptors is an accessible method of cancer detection and study.
Nucleic Acid versus Protein Markers
Molecular cancer biomarkers can be nucleic acids or proteins that, through their expression, define germline or somatic cell variation, transcriptional changes, and more. Nucleic acid markers are genetic or epigenetic changes in DNA or RNA of a cell; broadly, cancer develops as a result of the inappropriate translation and expression of DNA/RNA. Changes in DNA/RNA behavior can be highly specific to certain cancers. Increasing the complexity with which we understand these markers can increase the precision achieved in ongoing cancer prognosis and treatments. BioChain carries tissues characterized for nucleic acid biomarkers such as BRCA1 and 2; abnormal activity in these genes is commonly associated with ovarian, breast, and other cancers.
Protein markers can be slightly more complex due to their sensitivity to physiological changes and their post-translational function. Put plainly, there are a few more conditions or variables between protein function and expression and cancer prediction and prognosis as compared to their nucleic acid counterparts. BioChain’s high quality protein samples are used in research as reference materials for predictive and prognostic measurement of protein expression in diseased and normal tissue.
Characterizing for Cancer Biomarkers
To successfully be used in cancer research, tissue samples must first be characterized. BioChain characterizes its tissues using a few different techniques. Techniques such as PCR, microarray analysis, and next-generation sequencing (NGS) are used to characterize the genetic and epigenetic features of tissue samples, identifying mutations, gene expression patterns, and other molecular alterations. These techniques are most commonly seen in our CancerSeq line.
Our immunohistochemistry (IHC) techniques use antibodies to detect specific proteins in tissue sections, allowing for the identification of particular cell types or the presence of disease markers.
At BioChain, we also spatially characterize our tissue samples, which involves characterizing the tissue at the single cell level. Spatial characterization captures exponentially more marker information than NGS techniques can and provides contextual information about the interactions of those genes and proteins’ expression and behavior within the cell.
CancerSeq: BioChain’s Cancer-Specific Biomarker Line
At BioChain, we carry a cancer-specific line of formalin-fixed, paraffin-embedded (FFPE) that have been characterized using NGS techniques for specific cancer mutations. This means that the tissues themselves are selected according to cancer relevance, and the data associated with each sample is considerate of cancer-specific biomarkers. Called our CancerSeq line, these tissues and the data they carry can be used by clinicians and scientists as positive controls in molecular and genomic cancer research.
BioChain offers two lines of cancer-specific characterized tissue: CancerSeq and CancerSeq Plus. Both lines use a range of FFPE tissues, including colon, breasts, lung, stomach, and ovary. They are differentiated by the panels used to characterize the tissue.
CancerSeq uses an Illumina panel with 48 characterized genes, while CancerSeq Plus uses an Archer DX panel that covers approximately 65 different characterized genes. Accompanying each panel is all the associated gene data, characterized using Next Generation Sequencing.
Applications of BioChain Samples in Cancer Research
BioChain’s samples are designed for use in validation studies or drug testing as controls.
Example 1: Profiling Cellular and Immunologic Heterogeneity of Lung Cancer Cells
A study on the immunogenicity of small cell lung carcinoma (SCLC) used BioChain’s characterized SCLC FFPE samples in order to better profile the cancer’s plasticity and learn about its response to treatments that encourage immune rejection. The study found that a specific type of SCLC, which doesn’t behave like typical nerve-related cells, can trigger the body’s immune system to attack the cancer by making it easier for certain immune cells like CD8+T cells to recognize and fight the tumor. Patients with this type of SCLC, where these immune markers are high, may respond better to certain types of immunotherapy. This suggests that these immune markers could be useful in identifying which patients might benefit most from this therapy, especially in cases where other treatments haven’t worked.
Example 2: Exome Sequencing of the Neuronal Gene Biomarker CADM1 in Non-Cancerous Adrenal Tumors
Aldosterone-producing adenoma (APA) is a non-cancerous adrenal tumor that is a common cause of hypertension. One of the genetic markers of smaller, more difficult to detect APAs is pathogenic mutation of the cell adhesion molecule 1, or CADM1 gene. In a recent study, researchers used BioChain’s human lung mRNA samples as controls to report on the phenotype and replication of CADM1 mutation across different APA cohorts.
Molecular biomarkers are a cornerstone of modern cancer research and have revolutionized the development and research of genetically-tailored cancer treatments. Ongoing access to and work with cancer biomarkers has huge implications for the continued innovation of cancer therapies with reduced toxicity and higher efficacy. BioChain’s in-house pathologists characterize wide, diverse ranges of FFPE and frozen tissue for use as controls in validation studies. Depending on the needs of your study, we offer tissues characterized for cancer biomarkers using NGS, spatial, and IHC techniques.
Contact us today if you’re interested in learning more about BioChain’s CancerSeq, CancerSeq Plus, or spatially-characterized tissue samples today!
