Telomere and telomerase: Traditional tumor targets regain their applications for liver cancer diagnosis and prognosis

Table 1 Comprehensive comparison of telomere-based diagnostic biomarkers for hepatocellular carcinoma[30,31,51-56]

Biomarker type	Sample source	Detection method	Sensitivity (%)	Specificity (%)	AUC	Clinical readiness	Ref.
Peripheral blood leukocyte telomere length	Peripheral blood	qPCR	40-65	60-80	Approximately 0.65	Clinical research phase	Liu et al[51]; Ma et al[52]
Circulating tumor DNA telomere length	Plasma	qPCR, NGS	70-85	80-90	0.80-0.87	Advanced clinical research	Campani et al[53]
Telomere fusions in plasma	Plasma	NGS	Approximately 90 (advanced HCC)	Approximately 95	NA	Early clinical research	Maciejowski and de Lange[30]
Circulating telomerase-positive cells	Peripheral blood	TRAP assay, FISH-flow cytometry	60-75	85-95	Approximately 0.85	Exploratory/technology development	Zhang et al[31]; Sapi et al[54]
Tissue TERT promoter mutations	Tumor tissue	Sanger sequencing, ddPCR, NGS	Approximately 60	Approximately 100	NA	Used for molecular subtyping/clinical research	Lombardo et al[55]
Multi-analyte integrated panel (e.g., ctDNA TL + TERT mutation + AFP)	Plasma/blood	Combination of methods	85-95	90-95	0.90-0.95	Cutting-edge exploratory/validation phase	Akuta et al[56]

AUC: Area under the receiver operating characteristic curve; AFP: Alpha-fetoprotein; ctDNA: Circulating tumor DNA; TL: Telomere length; qPCR: Quantitative polymerase chain reaction; NGS: Next-generation sequencing; TRAP: Telomeric repeat amplification protocol; FISH: Fluorescence in situ hybridization; ddPCR: Droplet digital polymerase chain reaction; HCC: Hepatocellular carcinoma; NA: Not applicable.