Discovery, Validation, and Application of Novel Methylated DNA Markers for Detection of Esophageal Cancer in Plasma.
Aged
Biomarkers, Tumor
/ blood
Case-Control Studies
DNA Methylation
Early Detection of Cancer
/ methods
Epigenome
Esophageal Neoplasms
/ blood
Female
Humans
Male
Middle Aged
ROC Curve
Rho Guanine Nucleotide Exchange Factors
/ blood
Sialyltransferases
/ blood
T-Box Domain Proteins
/ blood
Tumor Suppressor Proteins
/ blood
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 12 2019
15 12 2019
Historique:
received:
05
03
2019
revised:
20
06
2019
accepted:
11
09
2019
pubmed:
19
9
2019
medline:
27
10
2020
entrez:
19
9
2019
Statut:
ppublish
Résumé
The burden of esophageal cancer continues to rise, and noninvasive screening tools are needed. Methylated DNA markers (MDM) assayed from plasma show promise in detection of other cancers. For esophageal cancer detection, we aimed to discover and validate MDMs in tissue, and determine their feasibility when assayed from plasma. Whole-methylome sequencing was performed on DNA extracted from 37 tissues (28 EC; 9 normal esophagus) and 8 buffy coat samples. Top MDMs were validated by methylation specific PCR on tissue from 76 EC (41 adeno, 35 squamous cell) and 17 normal esophagus. Quantitative allele-specific real-time target and signal amplification was used to assay MDMs in plasma from 183 patients (85 EC, 98 controls). Recursive partitioning (rPART) identified MDM combinations predictive of esophageal cancer. Validation was performed From discovery, 23 candidate MDMs were selected for independent tissue validation; median area under the receiver operating curve (AUC) for individual MDMs was 0.93. Among 12 MDMs advanced to plasma testing, rPART modeling selected a 5 MDM panel ( Novel MDMs assayed from plasma detect esophageal cancer with moderate accuracy. Further optimization and clinical testing are warranted.
Identifiants
pubmed: 31527170
pii: 1078-0432.CCR-19-0740
doi: 10.1158/1078-0432.CCR-19-0740
pmc: PMC6911634
mid: NIHMS1540205
doi:
Substances chimiques
ARHGEF4 protein, human
0
Biomarkers, Tumor
0
Rho Guanine Nucleotide Exchange Factors
0
T-Box Domain Proteins
0
TBX15 protein, human
0
Tumor Suppressor Proteins
0
ZNF671 protein, human
0
Sialyltransferases
EC 2.4.99.-
alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
EC 2.4.99.8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
7396-7404Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR000136
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA214679
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA163060
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002377
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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