- Biomarkers in blood are measurable biological molecules or entities detected in plasma, serum, or whole blood that provide insights into physiological states, disease processes, or responses to therapeutic interventions.
- Blood-based biomarkers are widely used in clinical practice due to their accessibility, obtained through relatively non-invasive venipuncture, and their ability to reflect systemic or organ-specific changes. These biomarkers include proteins, nucleic acids, metabolites, lipids, and circulating cells, offering applications in diagnosis, prognosis, monitoring, and prediction of treatment outcomes across diverse conditions such as cancer, cardiovascular diseases, neurodegenerative disorders, and inflammatory demyelinating diseases.
- The development and validation of blood biomarkers require advanced analytical technologies and rigorous testing to ensure specificity, sensitivity, and reproducibility, addressing challenges like biological variability and sample handling to enhance their clinical utility.
- Proteins are among the most established blood-based biomarkers, reflecting disease-specific or pathological processes. For instance, cardiac troponins (e.g., troponin I and T) are highly specific for myocardial injury, serving as diagnostic biomarkers for acute myocardial infarction. In oncology, prostate-specific antigen (PSA) in serum aids in prostate cancer screening, while CA-125 is used for ovarian cancer. In neurological disorders, neurofilament light chain (NfL), a marker of axonal damage, is increasingly measured in blood as a diagnostic and monitoring biomarker for multiple sclerosis (MS), Alzheimer’s disease, and traumatic brain injury. Inflammatory markers like C-reactive protein (CRP) and interleukin-6 (IL-6) indicate systemic inflammation, guiding diagnosis in infections, autoimmune diseases, and cardiovascular risk assessment. Autoantibodies, such as aquaporin-4 immunoglobulin G (AQP4-IgG) for neuromyelitis optica spectrum disorder (NMOSD), are critical for distinguishing specific autoimmune conditions from similar disorders.
- Nucleic acids, including circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and microRNAs (miRNAs), are emerging as powerful blood-based biomarkers, particularly in oncology and prenatal screening. ctDNA carrying tumor-specific mutations, such as EGFR in lung cancer, enables non-invasive cancer diagnosis and monitoring of treatment resistance. cfDNA analysis in pregnant women detects fetal genetic abnormalities, serving as a non-invasive prenatal test. miRNAs, small non-coding RNAs, regulate gene expression and are dysregulated in diseases like cancer, cardiovascular disease, and neurodegenerative disorders, offering diagnostic and prognostic potential. However, their clinical adoption is limited by challenges in standardization and sensitivity of detection methods. Methylation patterns in cfDNA are also serve as epigenetic biomarkers, with applications in early cancer detection and tissue-of-origin identification.
- Metabolites and lipids in blood provide additional diagnostic and monitoring insights. For example, elevated low-density lipoprotein cholesterol (LDL-C) levels are a well-established biomarker for cardiovascular risk, while HbA1c reflects long-term glycemic control in diabetes. Inborn errors of metabolism, such as phenylketonuria, are diagnosed using blood levels of specific amino acids like phenylalanine. Lipidomic profiling identifies dysregulated lipid species in diseases like Alzheimer’s, where altered ceramide levels may reflect early pathology. Circulating metabolites, detected through metabolomics, are also explored for sepsis, where lactate levels serve as a biomarker of tissue hypoxia, guiding resuscitation efforts. These small molecules offer a snapshot of metabolic activity, complementing other biomarker classes.
- Circulating cells or cellular components in blood, such as circulating tumor cells or extracellular vesicles, are gaining attention as biomarkers. Circulating tumor cells (CTCs) are used in blood to detect metastatic cancers, though their rarity requires ultrasensitive detection methods like flow cytometry or microfluidics. Platelet counts and function serve as biomarkers in hematological disorders, while white blood cell counts guide infection management. Extracellular vesicles, such as exosomes, carry proteins and nucleic acids, offering potential biomarkers for cancer and neurological disorders. Analytical platforms like enzyme-linked immunosorbent assay (ELISA), mass spectrometry, polymerase chain reaction (PCR), and next-generation sequencing drive biomarker discovery, but challenges include assay variability, pre-analytical factors (e.g., sample storage), and biological influences like age or comorbidities. Regulatory approval demands robust validation, as seen with companion diagnostics in precision medicine.
- In summary, blood-based biomarkers are pivotal in modern diagnostics, offering a non-invasive window into health and disease. Their diversity spans—proteins, nucleic acids, metabolites, and cells—enables applications across medical fields, from early detection to personalized therapy. Advances in analytical technology are expanding their scope, but standardization and validation remain critical to overcome limitations. By providing actionable insights with minimal invasiveness, blood biomarkers are transforming clinical practice and research, promising further breakthroughs in precision medicine.
