PT  - JOURNAL ARTICLE
AU  - TOSHIAKI HAGIWARA
AU  - KIICHI SUGIMOTO
AU  - HIROTAKA MOMOSE
AU  - TAKAHIRO IRIE
AU  - KUMPEI HONJO
AU  - YU OKAZAWA
AU  - MASAYA KAWAI
AU  - SHINGO KAWANO
AU  - SHINYA MUNAKATA
AU  - MAKOTO TAKAHASHI
AU  - YUTAKA KOJIMA
AU  - NOBUKO SERIZAWA
AU  - AKIHITO NAGAHARA
AU  - ROBERT M. HOFFMAN
AU  - MALCOLM V. BROCK
AU  - KAZUHIRO SAKAMOTO
TI  - CHFR-Promoter-Methylation Status Is Predictive of Response to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal Cancer
AID  - 10.21873/anticanres.15528
DP  - 2022 Feb 01
TA  - Anticancer Research
PG  - 697--707
VI  - 42
IP  - 2
4099  - http://ar.iiarjournals.org/content/42/2/697.short
4100  - http://ar.iiarjournals.org/content/42/2/697.full
SO  - Anticancer Res2022 Feb 01; 42
AB  - Background/Aim: 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: 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: 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: Sensitivity of advanced CRC patients to irinotecan-based systemic chemotherapy can be predicted by the extent of CHFR-promoter methylation.