Implementable assay for monitoring minimum residual disease after radical treatment for colorectal cancer

Takafumi Nakano, Seiichiro Takao, Katsushi Dairaku, Naoki Uno, Siew Kee Low, Masahiro Hashimoto, Yasuo Tsuda, Yuichi Hisamatsu, Takeo Toshima, Yusuke Yonemura, Takaaki Masuda, Ken Eto, Toru Ikegami, Yosuke Fukunaga, Atsushi Niida, Satoshi Nagayama, Koshi Mimori

Research output: Contribution to journalArticlepeer-review

Abstract

Considering the cost and invasiveness of monitoring postoperative minimal residual disease (MRD) of colorectal cancer (CRC) after adjuvant chemoradiotherapy (ACT), we developed a favorable approach based on methylated circulating tumor DNA to detect MRD after radical resection. Analyzing the public database, we identified the methylated promoter regions of the genes FGD5, GPC6, and MSC. Using digital polymerase chain reaction (dPCR), we termed the “amplicon of methylated sites using a specific enzyme” assay as “AMUSE.” We examined 180 and 114 pre- and postoperative serial plasma samples from 28 recurrent and 19 recurrence-free pathological stage III CRC patients, respectively. The results showed 22 AMUSE-positive of 28 recurrent patients (sensitivity, 78.6%) and 17 AMUSE-negative of 19 recurrence-free patients (specificity, 89.5%). AMUSE predicted recurrence 208 days before conventional diagnosis using radiological imaging. Regarding ACT evaluation by the reactive response, 19 AMUSE-positive patients during their second or third blood samples showed a significantly poorer prognosis than the other patients (p = 9E-04). The AMUSE assay stratified four groups by the altered patterns of tumor burden postoperatively. Interestingly, only 34.8% of cases tested AMUSE-negative during ACT treatment, indicating eligibility for ACT. The AMUSE assay addresses the clinical need for accurate MRD monitoring with universal applicability, minimal invasiveness, and cost-effectiveness, thereby enabling the timely detection of recurrences. This assay can effectively evaluate the efficacy of ACT in patients with stage III CRC following curative resection. Our study strongly recommends reevaluating the clinical application of ACT using the AMUSE assay.

Original languageEnglish
Pages (from-to)1989-2001
Number of pages13
JournalCancer Science
Volume115
Issue number6
DOIs
Publication statusPublished - Jun 2024
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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