Table 1.

Categories of biomarkers and diseases for which different markers have clinical relevance

Types of Biomarkers	Definition	Application	Diseases for Clinical Relevance	References
Diagnostic Biomarker	A biomarker used to detect or confirm presence of a disease or condition of interest, alternatively, to identify individuals with a subtype of the disease	Histology/ Histopathology IDH1/2 mutation 1p/19q codeletion TERT gene promoter mutation MGMT promoter methylation	Oligodendrogliomas: 1p/19q codeletion Glioblastomas: MGMT promoter methylation Gliomas: TERT promoter mutation	[26–31]
Monitoring Biomarker	A biomarker measured continuously for evaluating status of a disease or medical condition or for evidence of exposure to (or effect of) a medical product or an environmental agent	Contrast enhanced MRI brain Circulating exosomes Circulating microRNAs	Brain tumor: MRI Contrast enhanced tumor/nontumor enhancing tissues Brain metastases: Cancer-derived exosomes for Immune interactions and therapeutic implications Chronic lymphocytic leukemia (lymphoid malignancy): MicroRNAs (miRNAs) are a class of small noncoding RNAs	[32–36]
Pharmacodynamic Biomarker / Response Biomarker	Pharmacodynamic and response biomarkers use to reveal that biological response or latently advantageous or harmful, has occurred in an individual who has been exposed to a medical product or an environmental agent As a pharmacodynamic biomarker pharmacologic response in humans, or surrogate endpoint of earlier-phase it depends on characteristic mark by the level of clinical validation	Contrast enhanced MRI brain Reduced malignant cell count in CSF cytology/flow cytometry 18F-FDG PET	Brain tumor,metastases in neuroimaging: MRI Contrast enhanced tumor/nontumor enhancing tissues Occult leptomeningeal disease, malignant hematopoietic cells: CNS involvement, cancer cells in the CSF Glioblastoma: Radiopharmaceuticals evaluated in clinical studies for oncology, pharmacodynamic biomarker	[37–49]
Predictive Biomarker	A biomarker used to identify individuals who are more probably than similar individuals without the biomarker to experience an advantageous or disadvantageous effect from exposure to a medical product or an environmental agent	IDH1/2 mutation 1p/19q codeletion MGMT promoter methylation	Glioma: IDH1/2 mutation Oligodendrogliomas: 1p/19q codeletion Glioblastomas: MGMT promoter methylation	[17, 50, 51]
Prognostic biomarker	A biomarker used to identify likelihood of a clinical event, disease recurrence or progression in patients who have the disease or medical condition of interest	IDH1/2 mutation 1p/19q codeletion MGMT promoter methylation SHH gene pathway mutations, Chromosome 17p deletions and TP53 mutations	Glioma: IDH1/2 mutation Oligodendrogliomas: 1p/19q codeletion Glioblastomas: MGMT promoter methylation Medulloblastoma: SHH gene pathway mutations	[52–57]
Susceptibility/Risk Biomarker	A biomarker that reveals the potential for progressing a disease or medical condition in an individual who does not currently have clinically obvious disease or the medical condition	Inherited genetic disorders APOE gene variations DNA repair gene polymorphisms	Alzheimer's disease: APOE genotype	[58, 59]
Safety Biomarker	A biomarker measured before or after an exposure to a medical product or an environmental agent to reveal the likelihood, existence, or range of toxicity as an adverse effect	Complete blood cell count Genetic polymorphisms	Gliomas: Evaluating preoperative complete blood cell count-derived inflammatory biomarkers Diffuse glioma: MGMT gene polymorphisms with myelotoxicity, severe hematological toxicity treated with TMZ	[60, 61]
Validated Surrogate Endpoint	An endpoint supported by an obvious mechanistic rationale and clinical data providing strong evidence that an effect on the surrogate endpoint predicts a specific clinical advantage	Progression-free survival Time-to-progression	Tumor correlate with overall survival in progression-free survival Randomization to tumor progression or death in time-to-progression	[62–64]

These criteria are defined on the basis of the FDA-NIH biomarker working group and contents of a biomarker description [6]