Prediction of Efficacy of Postoperative Chemotherapy by DNA Methylation of CDO1 in Gastric Cancer.
Age Factors
Aged
Aged, 80 and over
Antineoplastic Agents
/ pharmacology
Biomarkers, Tumor
/ genetics
Cell Line, Tumor
Chemotherapy, Adjuvant
/ methods
Cysteine Dioxygenase
/ genetics
DNA Methylation
Drug Combinations
Drug Resistance, Neoplasm
/ genetics
Epigenesis, Genetic
Female
Follow-Up Studies
Gastrectomy
Humans
Kaplan-Meier Estimate
Male
Neoplasm Recurrence, Local
/ epidemiology
Neoplasm Staging
Oxonic Acid
/ pharmacology
Prognosis
Promoter Regions, Genetic
/ genetics
Retrospective Studies
Risk Factors
Stomach
/ pathology
Stomach Neoplasms
/ genetics
Tegafur
/ pharmacology
CDO1
Chemosensitivity
Chemotherapy
DNA methylation
Gastric cancer
Prognosis
Journal
The Journal of surgical research
ISSN: 1095-8673
Titre abrégé: J Surg Res
Pays: United States
ID NLM: 0376340
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
08
03
2020
revised:
08
07
2020
accepted:
11
07
2020
pubmed:
11
8
2020
medline:
13
3
2021
entrez:
11
8
2020
Statut:
ppublish
Résumé
CDO1 is a presumed tumor suppressor gene in human cancers, the expression of which is silenced by promoter DNA methylation. Moreover, CDO1 harbors functionally oncogenic aspects through modification of mitochondrial membrane potential. We recently proposed that this oncogenic feature allows for the prediction of the efficacy of postoperative chemotherapy in colon cancer. The present study aims to elucidate the efficacy of prediction of success of postoperative chemotherapy in advanced gastric cancer to improve the treatment strategy of patients. Forced expression of CDO1 in gastric cancer cell lines was assessed using the JC-1 assay. Promoter DNA methylation was investigated in quantitative TaqMan methylation-specific polymerase chain reaction in 321 pathological stage II/III advanced gastric cancer cases treated by curative gastrectomy with or without postoperative chemotherapy. (1) Forced expression of CDO1 led to increased mitochondrial membrane potential, accompanied by augmented survival in gastric cancer cells under anaerobic conditions. These results suggest that CDO1-expressing cancer cells survive more easily in anaerobic lesions which are inaccessible to anticancer drugs. (2) Intriguingly, in cases with the highest CDO1 methylation (ranging from 15% to 40%), patients with postoperative chemotherapy showed significantly better survival than those with no postoperative chemotherapy. (3) A robust prognostic difference was observed that was explained by differential recurrences of distant metastasis (P = 0.0031), followed by lymph node (P = 0.0142) and peritoneal dissemination (P = 0.0472). The oncogenic aspects of CDO1 can be of use to determine patients with gastric cancer who will likely respond to treatment of invisible systemic dissemination by postoperative adjuvant chemotherapy.
Sections du résumé
BACKGROUND
CDO1 is a presumed tumor suppressor gene in human cancers, the expression of which is silenced by promoter DNA methylation. Moreover, CDO1 harbors functionally oncogenic aspects through modification of mitochondrial membrane potential. We recently proposed that this oncogenic feature allows for the prediction of the efficacy of postoperative chemotherapy in colon cancer. The present study aims to elucidate the efficacy of prediction of success of postoperative chemotherapy in advanced gastric cancer to improve the treatment strategy of patients.
MATERIALS AND METHODS
Forced expression of CDO1 in gastric cancer cell lines was assessed using the JC-1 assay. Promoter DNA methylation was investigated in quantitative TaqMan methylation-specific polymerase chain reaction in 321 pathological stage II/III advanced gastric cancer cases treated by curative gastrectomy with or without postoperative chemotherapy.
RESULTS
(1) Forced expression of CDO1 led to increased mitochondrial membrane potential, accompanied by augmented survival in gastric cancer cells under anaerobic conditions. These results suggest that CDO1-expressing cancer cells survive more easily in anaerobic lesions which are inaccessible to anticancer drugs. (2) Intriguingly, in cases with the highest CDO1 methylation (ranging from 15% to 40%), patients with postoperative chemotherapy showed significantly better survival than those with no postoperative chemotherapy. (3) A robust prognostic difference was observed that was explained by differential recurrences of distant metastasis (P = 0.0031), followed by lymph node (P = 0.0142) and peritoneal dissemination (P = 0.0472).
CONCLUSIONS
The oncogenic aspects of CDO1 can be of use to determine patients with gastric cancer who will likely respond to treatment of invisible systemic dissemination by postoperative adjuvant chemotherapy.
Identifiants
pubmed: 32777557
pii: S0022-4804(20)30456-X
doi: 10.1016/j.jss.2020.07.001
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
Drug Combinations
0
S 1 (combination)
150863-82-4
Tegafur
1548R74NSZ
Oxonic Acid
5VT6420TIG
CDO1 protein, human
EC 1.13.11.20
Cysteine Dioxygenase
EC 1.13.11.20
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
404-412Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.