Prognostic utility of circulating tumor DNA methylation analysis in stage IV colorectal cancer

Author:

Momose Hirotaka1,Sugimoto Kiichi1ORCID,Irie Takahiro1,Nomura Sachio2,Ro Hisashi1,Ishiyama Shun1,Takahashi Makoto1,Pisanic Thomas3,Sakamoto Kazuhiro1

Affiliation:

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

2. Department of Pathology and Oncology Juntendo University Faculty of Medicine Tokyo Japan

3. Institute for NanoBioTechnology Johns Hopkins University Baltimore Maryland USA

Abstract

AbstractBackground and ObjectivesOur aim in this study was to investigate the usefulness of circulating tumor (ct) DNA methylation analysis for predicting long‐term outcomes after resection in Stage IV colorectal cancer (CRC).MethodsMethylation analyses were performed on 95 plasma samples from patients with CRC who underwent surgery. The methylation status (relative methylation value: RMV) of CpG within the promoter region of three genes (CHFR, SOX11, and CDO1) was assessed to quantitative methylation‐specific PCR (qMSP) analysis.ResultsIn the patients who had undergone resection of the primary tumor and metastatic organs with curative intent, the CHFR‐RMV high group had significantly worse recurrence‐free survival (RFS) compared with the CHFR‐RMV low group (p = 0.001). Multivariate analysis revealed that CHFR‐RMV was a significant independent prognostic factor (hazard ratio = 2.63 (1.29–5.36); p = 0.008). In the patients who had undergone resection of the primary tumor with metastatic organs with curative intent after neoadjuvant systemic chemotherapy, the SOX11‐RMV high group had significantly worse RFS compared with the SOX11‐RMV low group (p = 0.004).ConclusionsThe current study showed the usefulness of ctDNA methylation analysis for predicting the possibility of curative resection and long‐term outcomes after resection in Stage IV CRC. A future prospective study is needed to obtain more conclusive results.

Publisher

Wiley

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