Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction.
iScience
; 25(12): 105487, 2022 Dec 22.
Article
em En
| MEDLINE
| ID: mdl-36425756
ABSTRACT
Small-cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 patients with SCLC pre-treatment and from 20 non-cancer participants, genomic DNA (gDNA) from peripheral blood leukocytes from the same 74 patients, and 7 accompanying circulating tumor cell-derived xenografts (CDXs) underwent cfMeDIP-seq. Peripheral blood leukocyte methylation (PRIME) subtraction to improve tumor specificity. SCLC cfDNA methylation is distinct from non-cancer but correlates with CDX tumor methylation. PRIME and k-means consensus identified two methylome clusters with prognostic associations that related to axon guidance, neuroactive ligand-receptor interaction, pluripotency of stem cells, and differentially methylated at long noncoding RNA and other repeats features. We comprehensively profiled the SCLC methylome in a large patient cohort and identified methylome clusters with prognostic associations. Our work demonstrates the potential of liquid biopsies in examining SCLC biology encoded in the methylome.
Texto completo:
1
Base de dados:
MEDLINE
Tipo de estudo:
Guideline
/
Prognostic_studies
Idioma:
En
Revista:
IScience
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Canadá