Combination of CA19-9 and Blood Free-Circulating Methylated RUNX3 May Be Useful to Diagnose Stage I Pancreatic Cancer.
Adult
Aged
Aged, 80 and over
Antigens, Tumor-Associated, Carbohydrate
/ blood
Biomarkers, Tumor
/ blood
Core Binding Factor Alpha 3 Subunit
/ blood
DNA Methylation
/ genetics
Early Detection of Cancer
/ methods
Female
Humans
Male
Middle Aged
Neoplasm Staging
Pancreatic Diseases
/ blood
Pancreatic Neoplasms
/ blood
Polymerase Chain Reaction
/ methods
Prospective Studies
Sensitivity and Specificity
Biomarker
CA19-9
DNA methylation
Digital PCR
Pancreatic cancer
RUNX3
Journal
Oncology
ISSN: 1423-0232
Titre abrégé: Oncology
Pays: Switzerland
ID NLM: 0135054
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
09
2020
accepted:
21
09
2020
pubmed:
14
1
2021
medline:
15
4
2021
entrez:
13
1
2021
Statut:
ppublish
Résumé
Although serum carbohydrate antigen 19-9 (CA19-9) is widely used as a useful biomarker of pancreatic cancer for monitoring the response to therapy, it is not recommended for screening of early pancreatic cancer because of its limited sensitivity for small tumors. Thus, it is critical to discover novel serum biomarkers to complement CA19-9 in order to improve sensitivity. Although methylated runt-related transcription factor 3 (RUNX3) is a biomarker of pancreatic cancer, its detection by conventional bisulfite-based methylation assays from a small serum sample amount is very difficult. Therefore, we developed a new methylation assay, the combined restriction digital PCR (CORD) assay, that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. We evaluated the sensitivity and specificity of serum DNA testing of methylated RUNX3 by the CORD assay in combination with and without CA19-9 for the detection of pancreatic cancer in 55 patients with pancreatic cancer, 12 patients with benign pancreatic disease, and 80 healthy individuals. The CORD assay of methylated RUNX3 had a sensitivity of 50.9% (28/55) and specificity of 93.5% (86/92). Combination of the CORD assay of methylated RUNX3 and CA19-9 resulted in a sensitivity of 85.5% (47/55) and specificity of 93.5% (86/92) for all stages of pancreatic cancer and a sensitivity of 77.8% (7/9) for stage I pancreatic cancer. ombination of the CORD assay and CA19-9 may provide an alternative screening strategy for detecting early-stage pancreatic cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Although serum carbohydrate antigen 19-9 (CA19-9) is widely used as a useful biomarker of pancreatic cancer for monitoring the response to therapy, it is not recommended for screening of early pancreatic cancer because of its limited sensitivity for small tumors. Thus, it is critical to discover novel serum biomarkers to complement CA19-9 in order to improve sensitivity. Although methylated runt-related transcription factor 3 (RUNX3) is a biomarker of pancreatic cancer, its detection by conventional bisulfite-based methylation assays from a small serum sample amount is very difficult. Therefore, we developed a new methylation assay, the combined restriction digital PCR (CORD) assay, that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment.
OBJECTIVES
OBJECTIVE
We evaluated the sensitivity and specificity of serum DNA testing of methylated RUNX3 by the CORD assay in combination with and without CA19-9 for the detection of pancreatic cancer in 55 patients with pancreatic cancer, 12 patients with benign pancreatic disease, and 80 healthy individuals.
RESULTS
RESULTS
The CORD assay of methylated RUNX3 had a sensitivity of 50.9% (28/55) and specificity of 93.5% (86/92). Combination of the CORD assay of methylated RUNX3 and CA19-9 resulted in a sensitivity of 85.5% (47/55) and specificity of 93.5% (86/92) for all stages of pancreatic cancer and a sensitivity of 77.8% (7/9) for stage I pancreatic cancer.
CONCLUSIONS
CONCLUSIONS
ombination of the CORD assay and CA19-9 may provide an alternative screening strategy for detecting early-stage pancreatic cancer.
Identifiants
pubmed: 33440396
pii: 000511940
doi: 10.1159/000511940
doi:
Substances chimiques
Antigens, Tumor-Associated, Carbohydrate
0
Biomarkers, Tumor
0
Core Binding Factor Alpha 3 Subunit
0
Runx3 protein, human
0
carbohydrate antigen 199, human
0
Types de publication
Evaluation Study
News
Langues
eng
Sous-ensembles de citation
IM
Pagination
234-239Informations de copyright
© 2021 S. Karger AG, Basel.