Sugimoto Kiichi, Irie Takahiro, Momose Hirotaka, Kochi Saki, Toake Miyuki, Tsuchiya Yuki, Tsukamoto Ryoichi, Honjo Kumpei, Ishiyama Shun, Takahashi Makoto, Hoffman Robert M, Sakamoto Kazuhiro
Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan;
Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.
Anticancer Res. 2025 Apr;45(4):1559-1573. doi: 10.21873/anticanres.17537.
BACKGROUND/AIM: 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.
In the present study, there were 50 patients without preoperative treatment and 35 patients with preoperative treatment. Methylation analyses for checkpoint with forkhead and ring finger domains (), sex-determining region Y-box transcription factor 11 () and cysteine dioxygenase type 1 () used DNA extracted from plasma ctDNA at the time of resection of the primary tumor with curative-intent surgery.
Highly-methylated in ctDNA was found to be a biomarker of reduced recurrence-free survival (RFS) in LARC. In multivariate analysis, highly methylated was an independent prognostic factor for reduced RFS in the group without preoperative treatment.
The present study demonstrates that elevated ctDNA methylation of the gene is a biomarker for reduced RFS after curative-intent resection of LARC. Patients with high ctDNA methylation of the gene may not be optimal candidates for LARC resection. A prospective study is necessary to further validate ctDNA methylation as a biomarker for RFS of patients with LARC.
背景/目的:本研究旨在调查特定基因座的循环肿瘤DNA(ctDNA)甲基化情况,以预测局部晚期直肠癌(LARC)切除术后的长期预后。
在本研究中,有50例未接受术前治疗的患者和35例接受术前治疗的患者。使用从根治性手术切除原发性肿瘤时的血浆ctDNA中提取的DNA,对含叉头和环指结构域的检查点()、性别决定区Y盒转录因子11()和1型半胱氨酸双加氧酶()进行甲基化分析。
发现ctDNA中高度甲基化的是LARC中无复发生存期(RFS)降低的生物标志物。在多变量分析中,高度甲基化的是未接受术前治疗组中RFS降低的独立预后因素。
本研究表明,基因的ctDNA甲基化升高是LARC根治性切除术后RFS降低的生物标志物。基因ctDNA甲基化高的患者可能不是LARC切除的最佳候选者。有必要进行前瞻性研究,以进一步验证ctDNA甲基化作为LARC患者RFS生物标志物的作用。