Ultra-short cell-free DNA fragments enhance cancer early detection in a multi-analyte blood test combining mutation, protein and fragmentomics.
Clin Chem Lab Med
; 62(1): 168-177, 2024 01 26.
Article
en En
| MEDLINE
| ID: mdl-37678194
ABSTRACT
OBJECTIVES:
Cancer morbidity and mortality can be reduced if the cancer is detected early. Cell-free DNA (cfDNA) fragmentomics emerged as a novel epigenetic biomarker for early cancer detection, however, it is still at its infancy and requires technical improvement. We sought to apply a single-strand DNA sequencing technology, for measuring genetic and fragmentomic features of cfDNA and evaluate the performance in detecting multiple cancers.METHODS:
Blood samples of 364 patients from six cancer types (colorectal, esophageal, gastric, liver, lung, and ovarian cancers) and 675 healthy individuals were included in this study. Circulating tumor DNA mutations, cfDNA fragmentomic features and a set of protein biomarkers were assayed. Sensitivity and specificity were reported by cancer types and stages.RESULTS:
Circular Ligation Amplification and sequencing (CLAmp-seq), a single-strand DNA sequencing technology, yielded a population of ultra-short fragments (<100â¯bp) than double-strand DNA preparation protocols and reveals a more significant size difference between cancer and healthy cfDNA fragments (25.84â¯bp vs. 16.05â¯bp). Analysis of the subnucleosomal peaks in ultra-short cfDNA fragments indicates that these peaks are regulatory element "footprints" and correlates with gene expression and cancer stages. At 98â¯% specificity, a prediction model using ctDNA mutations alone showed an overall sensitivity of 46â¯%; sensitivity reaches 60â¯% when protein is added, sensitivity further increases to 66â¯% when fragmentomics is also integrated. More improvements observed for samples representing earlier cancer stages than later ones.CONCLUSIONS:
These results suggest synergistic properties of protein, genetic and fragmentomics features in the identification of early-stage cancers.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácidos Nucleicos Libres de Células
/
ADN Tumoral Circulante
/
Neoplasias
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Chem Lab Med
Asunto de la revista:
QUIMICA CLINICA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2024
Tipo del documento:
Article