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Session:: ePosters of Distinction: Potpourri

EPD516 - Circulating Tumor DNA Methylation Is A biomarker of Poor Recurrence-free Survival in Locally Advanced Rectal Cancer

Monday, May 11, 2026
5:03 PM - 5:08 PM ET

    ePoster of Distinction Presenter(s)

  • Kiichi Sugimoto, MD (he/him/his)

    Professor
    Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
    Juntendo University Faculty of Medicine
    Bunkyo-ku, Tokyo, Japan

    All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no relevant financial relationships.

    • Author(s)

  • Takahiro Irie, MD

    Undergraduate
    Department of Coloproctlogical Surgery, Juntendo University Faculty of Medicine
    Juntendo University
    Suginami-ku, Tokyo, Japan

    Disclosure information not submitted.

  • Saki Kochi, MD

    Graduate Student
    Department of Coloproctological Surgery, Juntendo University Faculty of Medicine
    Department of Coloproctological Surgery, Juntendo University Faculty of Medicine
    Tokyo, Tokyo, Japan

    Disclosure information not submitted.

  • Yuki Nakagawa, MD

    Graduate student
    Department of Coloproctological Surgery, Juntendo University Faculty of Medicine
    Juntendo University
    Bunkyo-ku, Tokyo, Japan

    Disclosure information not submitted.

Purpose/Background: Preoperative treatment (PT) for locally advanced rectal cancer (LARC) has improved postoperative outcomes. Regardless of the approach, LARC has a high local recurrence rate of 5-10% after radical resection. This background suggests the need for improvement of the indication for resection in LARC to improve long-term outcomes. Advances in detection of circulating tumor DNA (ctDNA) have facilitated the introduction of liquid biopsy assays into clinical practice. Hypermethylation of tumor suppressor genes can lead to cancer development and progression through gene silencing. The aim of this study was to investigate locus-specific circulating-tumor DNA (ctDNA) methylation for predicting long-term outcomes of locally advanced rectal cancer (LARC) after resection.

Methods/Interventions: There were 50 patients without preoperative treatment (no PT group) and 35 patients with preoperative treatment (PT group). Methylation analyses for checkpoint with forkhead and ring finger domains (CHFR), sex-determining region Y-box transcription factor 11 (SOX11) and cysteine dioxygenase type 1 (CDO1) used DNA extracted from plasma ctDNA at the time of resection of the primary tumor with curative-intent surgery. Long-term outcomes were evaluated based on recurrence-free survival (RFS).

Results/Outcomes: In the no PT group, there were no significant differences in RFS between CHFR-RMVhigh and -RMVlow (p=0.12) and CDO1-RMVhigh and -RMVlow (p=0.28) cases. However, SOX11-RMVhigh cases had a significantly worse RFS compared with SOX11-RMVlow cases (p < 0.0001). In the PT group, there were no significant differences in RFS between CHFR-RMVhigh and -RMVlow (p=0.20) and CDO1-RMVhigh and -RMVlow (p=0.25) cases. However, SOX11-RMVhigh cases again had significantly worse RFS compared with SOX11-RMVlow cases (p=0.04). In the no PT group, in which SOX11-RMVhigh cases had significantly worse RFS, a serum CEA level ≥5.0 ng/dl at the time of resection of the primary tumor was related to significantly worse RFS in univariate analysis (p=0.0004). Multivariate analysis with these two variables revealed that the serum CEA level at the time of resection of the primary tumor (HR=6.14, 95% CI=1.62-23.32; p=0.008) and SOX11-RMV (HR=8.59, 95%CI=2.33-31.71; p=0.001) were independent significant prognostic factors. In the PT group, in which SOX11-RMVhigh cases also had significantly worse RFS, no other factor was significantly related to worse RFS in univariate analysis. Therefore, multivariate analysis was not performed.

Conclusion/Discussion: The present study demonstrates that elevated ctDNA methylation of the SOX11 gene is a biomarker for reduced RFS after curative-intent resection of LARC. Patients with high ctDNA methylation of the SOX11 gene may not be optimal candidates for LARC resection. A prospective study is necessary to further validate SOX11 ctDNA methylation as a biomarker for RFS of patients with LARC.

RFS in high and low RMV cases in the no PT group
RFS in high and low RMV cases in the PT group