CHFR-Promoter-Methylation Status Is Predictive of Response to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal Cancer.

Biomarkers, Tumor / genetics Cell Cycle Proteins / genetics Colorectal Neoplasms / drug therapy DNA Methylation Female Humans Irinotecan / therapeutic use Male Neoplasm Proteins / genetics Poly-ADP-Ribose Binding Proteins / genetics Progression-Free Survival Promoter Regions, Genetic Topoisomerase I Inhibitors / therapeutic use Treatment Outcome Ubiquitin-Protein Ligases / genetics
Advanced colorectal cancer DNA-promoter methylation biomarker checkpoint-with-forkhead-and-ring-finger-domains (CHFR) clinical correlation histoculture drug response assay (HDRA) irinotecan

Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Feb 2022
Historique:
received: 08 11 2021
revised: 06 12 2021
accepted: 07 12 2021
entrez: 30 1 2022
pubmed: 31 1 2022
medline: 8 2 2022
Statut: ppublish

Résumé

We investigated whether promoter methylation of the checkpoint-with-forkhead-and-ring-finger-domains (CHFR) gene is a predictor of the efficacy of irinotecan-based systemic chemotherapy for advanced colorectal cancer (CRC) patients. CHFR-promoter methylation was measured by quantitative methylation-specific PCR (qMSP). The histoculture drug response assay (HDRA) was used in vitro to analyze the correlation between CHFR-promoter methylation and the efficacy of the irinotecan-active-metabolite SN38 in colorectal-cancer tissues from 44 CRC patients. CHFR promoter-methylation was also analyzed for its correlation with clinical response to irinotecan-based systemic chemotherapy of 49 CRC patients. CHFR-promoter methylation significantly-positively correlated with inhibition of colon cancer by SN38 in the HDRA (p=0.002). CHFR-promoter methylation also significantly-positively correlated with clinical response to irinotecan-based systemic chemotherapy (p=0.04 for disease control). CHFR-promoter methylation also significantly-positively correlated (p=0.01) with increased progression-free survival for patients treated with irinotecan-containing FLOFIRI in combination with bevacizumab, the most-frequent regimen in the cohort. Sensitivity of advanced CRC patients to irinotecan-based systemic chemotherapy can be predicted by the extent of CHFR-promoter methylation.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
We investigated whether promoter methylation of the checkpoint-with-forkhead-and-ring-finger-domains (CHFR) gene is a predictor of the efficacy of irinotecan-based systemic chemotherapy for advanced colorectal cancer (CRC) patients.
MATERIALS AND METHODS METHODS
CHFR-promoter methylation was measured by quantitative methylation-specific PCR (qMSP). The histoculture drug response assay (HDRA) was used in vitro to analyze the correlation between CHFR-promoter methylation and the efficacy of the irinotecan-active-metabolite SN38 in colorectal-cancer tissues from 44 CRC patients. CHFR promoter-methylation was also analyzed for its correlation with clinical response to irinotecan-based systemic chemotherapy of 49 CRC patients.
RESULTS RESULTS
CHFR-promoter methylation significantly-positively correlated with inhibition of colon cancer by SN38 in the HDRA (p=0.002). CHFR-promoter methylation also significantly-positively correlated with clinical response to irinotecan-based systemic chemotherapy (p=0.04 for disease control). CHFR-promoter methylation also significantly-positively correlated (p=0.01) with increased progression-free survival for patients treated with irinotecan-containing FLOFIRI in combination with bevacizumab, the most-frequent regimen in the cohort.
CONCLUSION CONCLUSIONS
Sensitivity of advanced CRC patients to irinotecan-based systemic chemotherapy can be predicted by the extent of CHFR-promoter methylation.

Identifiants

DOI: 10.21873/anticanres.15528 PMID: 35093868
pubmed: 35093868
pii: 42/2/697
doi: 10.21873/anticanres.15528
doi:

Substances chimiques

Biomarkers, Tumor 0
Cell Cycle Proteins 0
Neoplasm Proteins 0
Poly-ADP-Ribose Binding Proteins 0
Topoisomerase I Inhibitors 0
Irinotecan 7673326042
CHFR protein, human EC 2.3.2.27
Ubiquitin-Protein Ligases EC 2.3.2.27

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

697-707

Informations de copyright

Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Toshiaki Hagiwara (T)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Kiichi Sugimoto (K)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan; ksugimo@juntendo.co.jp.

Hirotaka Momose (H)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Takahiro Irie (T)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Kumpei Honjo (K)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Y U Okazawa (YU)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Masaya Kawai (M)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Shingo Kawano (S)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Shinya Munakata (S)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Makoto Takahashi (M)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Yutaka Kojima (Y)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Nobuko Serizawa (N)

Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Akihito Nagahara (A)

Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Robert M Hoffman (RM)

Department of Surgery, University of California San Diego and AntiCancer Inc, San Diego, CA, U.S.A.

Malcolm V Brock (MV)

Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.

Kazuhiro Sakamoto (K)

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du rectum › Tumeurs colorectales › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Composés hétérocycliques › Alcaloïdes › Camptothécine › Irinotécan › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines liant le poly-adp-ribose › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Survie sans progression › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Inhibiteurs des topoisomérases › Inhibiteurs de la topoisomérase-I › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › CHFR-Promoter-Methylation Status Is Predictive...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › CHFR-Promoter-Methylation Status Is Predictive...