Combination of CA19-9 and Blood Free-Circulating Methylated RUNX3 May Be Useful to Diagnose Stage I Pancreatic Cancer.


Journal

Oncology
ISSN: 1423-0232
Titre abrégé: Oncology
Pays: Switzerland
ID NLM: 0135054

Informations de publication

Date de publication:
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

234-239

Informations de copyright

© 2021 S. Karger AG, Basel.

Auteurs

Yuko Fujimoto (Y)

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Yutaka Suehiro (Y)

Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan, ysuehiro@yamaguchi-u.ac.jp.

Seiji Kaino (S)

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Shigeyuki Suenaga (S)

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Takanori Tsuyama (T)

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Hiroto Matsui (H)

Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Shingo Higaki (S)

Department of Gastroenterology, St. Hill Hospital, Ube, Japan.

Ikuei Fujii (I)

Department of Health Screening, Ajisu Kyoritsu Hospital, Yamaguchi, Japan.

Chieko Suzuki (C)

Department of Internal Medicine, Ajisu Kyoritsu Hospital, Yamaguchi, Japan.

Tomomi Hoshida (T)

Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Toshihiko Matsumoto (T)

Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Taro Takami (T)

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Hiroaki Nagano (H)

Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Isao Sakaida (I)

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Takahiro Yamasaki (T)

Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.

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