TABLE 2. Published studies with a reported specificity (≥ 80%) or Area Under the Curve (AUC, ≥0.9).
| Primary readout focus | Biospecimen | Effect on marker(s) | AUC (95% CI) | Sensitivity (%, 95% CI) | PMID |
|---|---|---|---|---|---|
| Protein, Peptides, or Post-translational Modification | Tissue | Tissue TOP1, PDIA4, and OGN expression profiles highly discriminatory | 98.2 | 35197484 | |
| Protein, Peptides, or Post-translational Modification | Blood | Panel of CA125, HE4, E-CAD, and IL-6 distinguished early stage HGSC from non-malignant controls with higher efficacy than CA125, HE4, or CA125+HE4 | 0.961 ± 0.0243 | 84.2 | 29572027 |
| Protein, Peptides, or Post-translational Modification | Blood | 84 up-regulated, 32 down-regulated proteins in serum from HGSC patients vs. healthy controls. | 0.99 | 100.0 | 35939567 |
| Protein, Peptides, or Post-translational Modification | Blood | Serum IL-6 distinguish between HGSC, benign ovarian masses, and non-malignant controls. Diagnostic value highest when IL-6 combined with CA125 and HE4. | IL-6: 0.962 (0.926–0.998) IL-6 + CA-125: 0.985 (0.966–1.000) IL-6 + HE4: 1.000 (1.000–1.000) | 32042020 | |
| Protein, Peptides, or Post-translational Modification | Blood | Combination of TNRF2+ Tregs and IL-6 in blood of advanced stage HGSC discriminates benign ovarian masses and non-malignant controls. | 1.000 (1.000–1.000) | 36765633 | |
| Protein, Peptides, or Post-translational Modification | Blood | Machine learning was able to predict EOC diagnosis and EOC stage based on several blood-born CRP, lymphocyte count, and CA125. | Conditional random forest: 0.978 Gradient based machine: 0.976 Random forest: 0.968 | 30979733 | |
| Protein, Peptides, or Post-translational Modification | Blood | Plasma ANXA2 elevated in early stage (I and II) HGSC compared to non-malignant controls. ANXA2 with CA125 test highly diagnostic of early stage OC. | 0.969 | 84.4 | 33406648 |
| Protein, Peptides, or Post-translational Modification | Blood | Serum Protein Z, fibronectin, CRP, and CA125 effective in predicting OC occurrence 2–3 years pre-diagnosis. | 0.944 (0.896–0.992) | 27903971 | |
| Protein, Peptides, or Post-translational Modification | Blood | Incorporating longitudinal measurement of serum CA125, HE4, CHI3L1, PEBP4, and/or AGR2 predicted OC (particularly HGSC) up to one year before diagnosis. | CA-125 + PEBP4: 0.97 (0.934–1.000) CA-125 + CHI3L1: 0.986 (0.973–0.999) CA-125 + AGR2 + CHI3L1: 0.984 (0.971–0.998) CA-125 + HE4: 0.988 (0.976–1.000) | CA-125 + PEBP4: 95.5 (77.3–100.0) CA-125 + CHI3L1: 100.0 (90.9–100.0) CA-125 + AGR2 + CHI3L1: 100.0 (90.9–100.0) CA-125 + HE4: 100.0 (86.4–100.0) |
31937926 |
| Protein, Peptides, or Post-translational Modification | Blood | Plasma antibodies against HSF1 and CCDC155 are elevated in early stage HGSC and are superior to CA125. Combined measurement improved sensitivity and efficacy of detection. | HSF1: 0.95 CCDC155: 0.80 | 29141850 | |
| Protein, Peptides, or Post-translational Modification | Blood | Increased serum MMP-9, Hpa, and CL levels in OC vs. healthy control and benign ovarian mass patients; low grade and advanced stage vs. high grade and early stage patients. | 0.935 | 96.4 | 23359763 |
| Protein, Peptides, or Post-translational Modification | Proximal Fluid | Increased GJA1, C4BPB, ATP2B4, VPS11, and TMEM67 expression and decreased KIF20B expression in HGSC proximal fluid vs. non-malignant control proximal fluid. | C4BPB + KIF20B: 0.979 (0.953–1.00) VPS11 + CRTAC1 + TMEM67: 0.968 (0.938–0.999) GJA1 + ATP2B4: 0.943 (0.889–0.997) | 36214786 | |
| Protein, Peptides, or Post-translational Modification | Blood, Proximal Fluid | Elevated serum and ovarian cyst fluid ALDOA diagnostic in early stage EOC (low grade and high grade) with (LC)-MS/MS. | 0.96 | 30710757 | |
| Protein, Peptides, or Post-translational Modification | Blood, Proximal Fluid | Serum and proximal fluid ADA upregulated in HGSC patients vs. patients with benign ovarian mass. | Serum ADA: 0.82 Peritoneal fluid ADA: 0.78 | Serum ADA: 84.0 Peritoneal fluid ADA: 74.0 | 22395862 |
| Protein, Peptides, or Post-translational Modification /DNA Mutational Profiles | Blood | Increased circulating histone-DNA complex, cfDNA, neutrophil elastase, prekallikrein, and CA125 in HGSC patients vs. healthy controls. | 0.966 (0.933–1.000) | 97.3 | 36620601 |
| Protein, Peptides, or Post-translational Modification /DNA Mutational Profiles | Blood, Proximal Fluid | Increased NETosis biomarkers (cfDNA, nucleosomes, cirtullinated histone 3, calprotectin, and myeloperoxidase) in serum and peritoneal fluid from HGSC patients vs. healthy controls. | cfDNA: 0.90 (0.80–1.00) Nucleosomes: 0.94 (0.87–1.00) citH3: 0.96 (0.92–1.00) Calprotectin: 0.91 (0.84–1.00) MPO: 0.87 (0.77–0.98) | 36817483 | |
| Epigenetics | Tissue | Whole methylome sequencing identified novel OC methylated-DNA- markers; differentiated 63/73 HGSC cases included 5/5 stage I/II cases. | 0.91 (0.86–0.96) | 79 (69–87) | 35370009 |
| Epigenetics | Tissue | Elevated methylation in promoter regions of TUBB6, IRX2, and c17orf64 in HGSC and precursor STICs compared to non-malignant controls. | 1.0 | 100.0 | 30108103 |
| Epigenetics | Tissue | Methylation landscape of STICs intermediate between normal FTE and HGSC tumors. | PCDHB12: 0.958 | 32817081 | |
| Epigenetics | Blood | Serum miR200a, b, and c higher in patients with serous EOC vs. non-malignant controls. Combo miR200b + c best predictive qualifier. | miR-200a: 0.675 miR-200b: 0.722 miR-200b + c: 0.784 | miR-200a: 85.7 miR-200b: 85.7 miR-200b + c: 78.6 | 23272653 |
| Epigenetics | Blood | Upregulated serum exosomal miR-93, miR-145, and miR-200c in HGSC samples compared to non-HGSC cases, benign, and borderline groups. Specificity and sensitivity superior to CA125. | miR-145: 0.910 (0.840–0.980) miR-200c: 0.802 (0.698–0.906) | miR-145: 91.7 miR-200c: 72.9 | 31205555 |
| Epigenetics | Blood | Model with 18 differentially methylated DNA regions (cfDNA) able to differentiate OC from non-malignant patients. | 0.967 (0.940–0.994) | 94.7 (85.4–98.9) | 35973389 |
| Epigenetics | Blood | miR-1246 overexpressed in both serum and tumors of HGSC patients vs. non-malignant controls. | 0.893 | 87 | 28017893 |
| Epigenetics | Blood, Cell line | Serum miR1290a elevated in HGSC compared to other histotypes and non-malignant controls. Serum levels more effective at detection than CA125 alone and positively associated with FIGO stage. | miR-1290: 0.71 CA-125 + miR-1290: 0.97 | miR-1290: 63 | 30219071 |
| Epigenetics/RNA | Tissue | Lower CDH13, HNF1B, PCDH17, and GATA4 gene expression in HGSC tumors vs. non-malignant control tissue, particularly in those samples with high gene methylation. | 88.5 | 32145055 | |
| Epigenetics/RNA | Blood | RASSF1A promoter methylation increased in EOC vs. healthy control; HGSC vs. LGHOC, advanced stage vs. early stage. | Serum RASSF1A: 0.993 (0.96–0.99) | Serum RASSF1A: 97 RASSF1A promoter methylation: 85 | 29098560 |
| DNA Mutational Profiles | Tissue | Using 49 different Copy Number Variant loci, can differentiate EOC from FT, AUC 1.0. | 1.00 (1.00–1.00) | 36499142 | |
| DNA Mutational Profiles | Blood | Comparing HGSC blood Copy Number Index-Score to that of healthy controls detects cancer. | 91.0 | 35008332 | |
| DNA Mutational Profiles | Blood | Higher plasma cfDNA in OC vs. non-malignant controls, positively associated with copy number alterations and FIGO stage. | 0.94 | 78.0 | 27852697 |
| DNA Mutational Profiles | Blood | Alterations in circulating cfDNA can be combined with CA125 to improve differential diganosis of OC. | 0.9752 | 96.0 | 34053311 |
| Metabolite | Blood | Alterations in several mouse serum metabolites detectable, differentiating between non-HGSC samples (control mice), early, and advanced HGSC (triple KO mice) | 96.2 | 31290664 | |
| Metabolite | Blood | Serum levels of 147 lipid species between HGSC patients and healthy controls; 100 species different between Stage I/II and controls. Lipid levels also varied by disease stage (I/II vs. III/IV). | 1.0 | 100.0 | 35495636 |
| Metabolite | Urine | Increased urine N1,N12-diacetylspermine levels in OC vs. tumor-free controls, HGSC vs. low malignant. Potential patients, stage III/IV vs. stage I/II, stage I/II vs. benign tumor patients. | 0.83 | 86.5 | 28604456 |
| Metabolite | Blood, Tissue | Increased plasma C16-Cer, C18:1-Cer, C18-Cer in HGSC ((+):: FIGO stage); increased tissue C16-Cer, C18:1-Cer, C18:Cer, C24:1-Cer, C24-Cer & SIP and decreased SPH in HGSC vs. normal tissue. | C18:1-Cer: 0.768 (0.53–0.81) C18-Cer: 0.771 (0.53–0.8) C16-Cer: 0.759 (0.51–0.8) | C18:1-Cer: 90.0 (59.6–98.5) C18-Cer: 80.0 (50.0–94.7) C16-Cer: 77.0 (56.5–94.3) | 28800942 |
| Metabolite/RNA | Blood, Tissue | Increased circulating lactate in HGSC patients, increased HCAR1 mRNA and protein expression in ovarian cancer tissue vs. healthy control. | 0.969 (0.940–0.998) | 36615018 | |
| Metabolite/RNA | Blood, Tissue, Public Dataset | Increased hydroxybutyric acid metabolites in sera and tumors from HGSC patients compared to non-malignant controls. | 0.91 | 26685161 |
Abbreviations: CA125 - cancer atnigen 125 or MUC16, EOC - epithelial ovarian cancer, FIGO - International Federation of Gynecology and Obstetrics, FT - fallopian tube, FTE - FT epithelium, HGSC - high grade serous carcinoma, mRNA - messenger RNA, miR - microRNA, OC - ovarian cancer