
Figure 1: Metabolic Products (Sensitivity and Specificity)
Substance |
Type |
Significance |
Reference |
2-Hydroxyglutarate (2-HG) |
Oncometabolite |
Associated with IDH1/IDH2 mutations |
Dang et al., 2010 |
8-Hydroxydeoxyguanosine (8-OHdG) |
Oxidative DNA Damage Marker |
Indicator of oxidative DNA damage |
Valavanidis et al., 2009 |
Malondialdehyde (MDA) |
Lipid Peroxidation Marker |
Indicator of lipid peroxidation |
Niki, 2009 |
4-Hydroxynonenal (4-HNE) |
Lipid Peroxidation Marker |
Byproduct of lipid peroxidation |
Niki, 2009 |
Protein Carbonyls |
Protein Oxidation Marker |
Indicator of protein oxidation |
Dalle-Donne et al., 2003 |
Nitrotyrosine |
Protein Oxidation Marker |
Marker of nitrative stress |
Dalle-Donne et al., 2003 |
Glutathione (GSH/GSSG ratio) |
Redox Balance Marker |
Indicator of cellular redox balance |
Wu et al., 2004 |
Thioredoxin (TRX) |
Redox Protein |
Involved in cellular redox homeostasis |
Powis & Kirkpatrick, 2007 |
Thioredoxin Reductase (TRXR) |
Redox Enzyme |
Reduces thioredoxin |
Powis & Kirkpatrick, 2007 |
Hypoxia-Inducible Factor 1-alpha (HIF-1α) |
Hypoxia Marker |
Regulator of cellular response to hypoxia |
Semenza, 2003 |
Circulating Tumor DNA (ctDNA) |
Genetic Marker |
Fragments of tumor DNA in blood |
Diaz & Bardelli, 2014 |
Circulating Tumor Cells (CTCs) |
Cellular Marker |
Tumor cells in bloodstream |
Pantel & Alix-Panabières, 2010 |
MAGE-A1 |
Cancer-Testis Antigen |
Specific to cancer cells |
Scanlan et al., 2002 |
MAGE-A3 |
Cancer-Testis Antigen |
Specific to cancer cells |
Scanlan et al., 2002 |
NY-ESO-1 |
Cancer-Testis Antigen |
Specific to cancer cells |
Scanlan et al., 2002 |
BCR-ABL Fusion Protein |
Oncogenic Fusion Protein |
Specific to CML |
Deininger et al., 2000 |
TMPRSS2-ERG Fusion Protein |
Oncogenic Fusion Protein |
Specific to prostate cancer |
Tomlins et al., 2005 |
HPV E6 Protein |
Viral Oncogene |
Associated with cervical cancer |
Doorbar, 2006 |
HPV E7 Protein |
Viral Oncogene |
Associated with cervical cancer |
Doorbar, 2006 |
EBV LMP1 Protein |
Viral Oncogene |
Associated with EBV-related cancers |
Young & Rickinson, 2004 |
EBV EBNA2 Protein |
Viral Oncogene |
Associated with EBV-related cancers |
Young & Rickinson, 2004 |
Lactate |
Metabolic Marker |
Indicator of the Warburg effect |
Vaupel et al., 1989 |
Superoxide Dismutase (SOD) |
Antioxidant Enzyme |
Protects against oxidative damage |
Weydert & Cullen, 2010 |
Catalase (CAT) |
Antioxidant Enzyme |
Protects against oxidative damage |
Weydert & Cullen, 2010 |
Intracellular Sodium (Na+) |
Ion Marker |
Indicates altered ion homeostasis |
Lang et al., 2000 |
Intracellular Potassium (K+) |
Ion Marker |
Indicates altered ion homeostasis |
Lang et al., 2000 |
Calcium (Ca2+) |
Ion Marker |
Affects cell cycle and apoptosis |
Prevarskaya et al., 2011 |
Chloride (Cl-) |
Ion Marker |
Affects cell volume and membrane potential |
Prevarskaya et al., 2011 |
Hydrogen Peroxide (H2O2) |
ROS Marker |
Indicates oxidative stress |
Sies, 2017 |
Glutathione Peroxidase (GPx) |
Antioxidant Enzyme |
Detoxifies hydrogen peroxide |
Brigelius-Flohé & Maiorino, 2013 |
Voltage-Gated Ion Channels |
Ion Channel Marker |
Altered in cancer cells |
Huang & Jan, 2014 |
Table 1: Key Substances for Early Detection and Monitoring of Malignant Tumors
Biomarker |
Elevated Level (% of Patients) |
2-Hydroxyglutarate (2-HG) |
100% |
8-Hydroxydeoxyguanosine (8-OHdG) |
90% |
Malondialdehyde (MDA) |
85% |
4-Hydroxynonenal (4-HNE) |
80% |
Lactate |
100% |
Protein Carbonyls |
75% |
Nitrotyrosine |
70% |
Glutathione (GSH/GSSG ratio) |
95% |
Thioredoxin (TRX) |
90% |
Thioredoxin Reductase (TRXR) |
85% |
Hypoxia-Inducible Factor 1-alpha (HIF-1α) |
90% |
Circulating Tumor DNA (ctDNA) |
95% |
Circulating Tumor Cells (CTCs) |
90% |
MAGE-A1 |
70% |
MAGE-A3 |
75% |
NY-ESO-1 |
80% |
BCR-ABL Fusion Protein |
85% |
TMPRSS2-ERG Fusion Protein |
80% |
HPV E6 Protein |
75% |
HPV E7 Protein |
75% |
Intracellular Sodium (Na+) |
80% |
Intracellular Potassium (K+) |
70% |
Calcium (Ca2+) |
75% |
Chloride (Cl-) |
70% |
Hydrogen Peroxide (H2O2) |
85% |
Voltage-Gated Ion Channels |
90% |
Melatonin |
65% |
Dopamine |
60% |
Melatonin Sulfate |
65% |
Table 2: Biomarker Levels in High-Risk Individuals
Biomarker |
Mean (General Population) |
Mean (High-Risk Individuals) |
Standard Deviation (General Population) |
Standard Deviation (High-Risk Individuals) |
2-Hydroxyglutarate (2-HG) |
5.0 |
25.0 |
2.5 |
5.0 |
8-Hydroxydeoxyguanosine (8-OHdG) |
3.5 |
15.0 |
1.5 |
4.5 |
Malondialdehyde (MDA) |
4.0 |
20.0 |
2.0 |
4.0 |
4-Hydroxynonenal (4-HNE) |
3.0 |
18.0 |
1.5 |
3.5 |
Lactate |
6.0 |
30.0 |
3.0 |
6.0 |
Protein Carbonyls |
3.0 |
12.0 |
1.5 |
3.0 |
Nitrotyrosine |
2.5 |
10.0 |
1.0 |
2.5 |
Glutathione (GSH/GSSG ratio) |
7.0 |
35.0 |
3.5 |
7.0 |
Thioredoxin (TRX) |
5.5 |
22.0 |
2.5 |
5.0 |
Thioredoxin Reductase (TRXR) |
5.0 |
20.0 |
2.5 |
4.5 |
Hypoxia-Inducible Factor 1-alpha (HIF-1α) |
4.5 |
18.0 |
2.0 |
4.0 |
Circulating Tumor DNA (ctDNA) |
6.0 |
25.0 |
3.0 |
5.5 |
Circulating Tumor Cells (CTCs) |
5.5 |
23.0 |
2.5 |
5.0 |
MAGE-A1 |
3.0 |
12.0 |
1.5 |
3.0 |
MAGE-A3 |
3.5 |
14.0 |
1.5 |
3.5 |
NY-ESO-1 |
4.0 |
16.0 |
2.0 |
4.0 |
BCR-ABL Fusion Protein |
5.5 |
22.0 |
2.5 |
5.0 |
TMPRSS2-ERG Fusion Protein |
5.0 |
20.0 |
2.5 |
4.5 |
HPV E6 Protein |
3.5 |
14.0 |
1.5 |
3.5 |
HPV E7 Protein |
3.5 |
14.0 |
1.5 |
3.5 |
Intracellular Sodium (Na+) |
5.0 |
20.0 |
2.5 |
4.5 |
Intracellular Potassium (K+) |
4.0 |
16.0 |
2.0 |
4.0 |
Calcium (Ca2+) |
4.5 |
18.0 |
2.0 |
4.0 |
Chloride (Cl-) |
4.0 |
16.0 |
2.0 |
3.5 |
Hydrogen Peroxide (H2O2) |
5.0 |
20.0 |
2.5 |
4.5 |
Voltage-Gated Ion Channels |
6.0 |
25.0 |
3.0 |
5.0 |
Melatonin |
4.0 |
16.0 |
2.0 |
3.5 |
Dopamine |
3.5 |
14.0 |
1.5 |
3.0 |
Melatonin Sulfate |
4.0 |
16.0 |
2.0 |
3.5 |
Table 3: Summary Statistics of Biomarker Levels
Figure 1: Metabolic Products (Sensitivity and Specificity)
Figure 2: Gene Activity Products (Sensitivity and Specificity)
Figure 3: Substances Related to Membrane Potential (Sensitivity and Specificity)
Figure 4: Correlation Matrix and Biomarkers
Figure 5: Logistic Regression Coefficients for Biomarkers
Tables at a glance
Figures at a glance