Table 2.
Quantitative performance of cfDNA-based liquid biopsy in the detection and TOO of cancer
| Classifier | No. of participants | Cancer | Sequencing approach | Sensitivity | Specificity | AUC | TOO |
|---|---|---|---|---|---|---|---|
| Cd-score82 | HCC (n = 1,098), healthy controls (n = 835) | HCC | Targeted bisulfite sequencing | Training, 85.7%; validation, 83.3% |
Training, 94.3%; validation, 90.5% |
Training, 0.966; validation, 0.944 |
NA |
| Wd-score83 | HCC (n = 1,204), CHB or liver cirrhosis (n = 392), benign liver lesions (n = 388), healthy controls (n = 570) | HCC | Genome-wide 5-hmC profiles | Training, 89.6%; vlidation-1, 82.7% |
Training, 78.9%; validation-1, 76.4% |
Training, 0.923; validation-1, 0.884; validation-2, 0.887 |
NA |
| HCC screen score84 | HCC (n = 65), CHB (n = 70); AFP/US-negative CHB (n = 331) | HCC | PCR | Training, 85.0%; validation, 100.0% |
Training, 93.5%; validation 94.0% |
Training, 0.928 validation, NA |
NA |
| HIFI score (5-hmC/motIf/Fragmentation/nucleosome footprInt)85 | HCC (n = 508), liver cirrhosis (n = 2,250), healthy controls (n = 476) | HCC | Low-pass WGS | Training, NA; test, 95.4%; validation, 95.8% |
Training, NA; test 97.8%; validation 95.0% |
Training, NA; test, 0.996; validation, 0.995 |
NA |
| cfDNA fragmentation86 | HCC (n = 159), ICC (n = 26), cHCC-ICC (n = 7); CHB or liver cirrhosis (n = 53), healthy controls (n = 117) | HCC, ICC, cHCC-ICC | WGS | Training, NA; test, 96.8% |
Training, NA; test, 98.8% |
Training, NA; test, 0.995 |
NA |
| Cd-score (9 methylation markers)87 | CRC (n = 801); healthy controls (n = 1,021) | CRC | Targeted methylation sequencing | Training, 87.5%; validation, 87.9% |
Training, 89.9%; validation, 89.6% |
Training, 0.960; validation, 0.960 |
NA |
| Multi-target stool DNA test composite score88 | Asymptomatic persons who were at average risk for CRC, aged 50–84 years (n = 9,989) | CRC | PCR | Total, 92.3%: stage I, 88.0%; stage II, 100%; stage III, 90.0%; stage IV, 78.0% | 86.6% | 0.940 | NA |
| PulmoSeek (Blood-based DNA methylation model)89 | Patients with pulmonary nodules (n = 529) | Lung cancer | Targeted methylation sequencing | Training, NA; Test, 93.3%; validation, 99.0% |
Training, NA; test, 60.0%; validation, 32.5% |
Training, NA; test, 0.829; validation, 0.843 |
NA |
| Lung-CLiP score55 | Early-stage NSCLC (n = 46), risk-matched healthy controls (n = 48) | Lung cancer | CAPP-seq | Training: stage I/II/III sensitivity: 41.0%, 54.0%, 67.0%; validation: stage I/II/III sensitivity: 63.0%, 69.0%, 75.0% | Training, 98.0%; validation, 80.0% | NA | |
| Methylation score90 | Plasma samples: RCC (n = 69), UBC (n = 21), healthy controls (n = 13); Urine samples: RCC (n = 30), healthy controls (n = 15) |
RCC, UBC | cfMeDIP-seq | NA | NA | Plasma, 0.990 (RCC vs healthy); plasma, 0.979 (RCC vs UBC); urine, 0.858 (RCC vs healthy) |
NA |
| LR score59 | Cancers (n = 414): post-diagnosis (n = 223), pre-diagnosis (n = 191) Healthy controls (n = 414) |
Stomach, esophageal, colorectal, lung, and liver cancers | Targeted methylation sequencing | Training: post-diagnosis, 88.2%; pre-diagnosis, 91.4%; test: post-diagnosis, 87.6%; pre-diagnosis, 94.9% | Training, 94.7%; test, 96.1% |
Training: NA; test: post-diagnosis, 0.970; pre-diagnosis 0.990 |
NA |
| Screen positive or negative91 | Chinese men aged 40–62 years (n = 20,174) | NPC | PCR | 97.1% | 98.6% | NA | |
| Circulating proteins and gene mutations (CancerSEEK)28 | Stages I‒III cancers (n = 1,005), healthy controls (n = 812) | Ovarian, liver, stomach, pancreatic, colorectal, lung, and breast, esophageal cancers | PCR | Median, 70.0% (range, 33.0% in breast cancer to 88.0% in ovarian cancer) | 99.1% | 0.910 | Top prediction: 39.0–84.0%; top 2 predictions: 63.0–100.0% |
| Circulating proteins and gene mutations + PET-CT/imaging92 | Women aged 65–75 years (n = 10,006) | Pan-cancer | PCR | 27.1% | 99.6% | NA | |
| Targeted methylation classifier93 | Cancers (n = 2,482), non-cancer (n = 4,207) | Multiple cancers (more than 50 types of cancer) | Targeted methylation assay | Training, 55.2%; validation, 54.9%; stage I, 18%; stage II, 43.0%; stage III, 81.0%; stage IV, 93.0% | Training, 99.8%; validation, 99.3% |
93.0% | |
| Targeted methylation classifier94 | Cancers (n = 2,823), non-cancer (n = 1,254) | Multiple cancers (6 types of cancer) | Targeted methylation assay | 51.5% | 99.5% | 88.7% | |
| cfDNA fragmentation patterns77 | Cancers (n = 236) and healthy controls (n = 245). | Breast, colorectal, stomach, lung, ovarian, pancreatic and biliary tract cancers | WGS | Stage I, 68.0%; stage II, 72.0%; stage III, 79.0%; stage IV, 77.0% | 98.0% | 0.940 | Top prediction: 61.0%; top two predictions: 75.0% |
Abbreviations: AUC, Area under curve; CHB, Chronic HBV infection; cHCC-ICC, Combined HCC and intrahepatic cholangiocarcinoma; ICC, Intrahepatic cholangiocarcinoma; Lung-CLiP, lung cancer likelihood in plasma; NPC, Nasopharyngeal carcinoma; NA, not available; PET-CT, Positron emission tomography/computed tomography; UBC, Urothelial bladder cancer; WGBS, Whole genome bisulfite sequencing.