Background and objective:Multiple markers have been proposed, but there are no reliable pre-treatment markers that predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer. The objective of this study is to evaluate the usefulness of pre-treatmentSEPTIN9gene methylation ratio as a predictor of tumor response to total neoadjuvant therapy and its correlation with tumor size and tumor stage in patients with locally advanced rectal cancer.Methods:Patients with locally advanced rectal cancer (T3/4 and/or N+ histologically confirmed rectal cancer) undergoing total neoadjuvant therapy were included. Tumor size and tumor stage were determined by magnetic resonance.SEPTIN9gene methylation in plasmatic cfDNA was analyzed by droplet digital PCR at the time of diagnosis. After completing total neoadjuvant therapy, tumor response was assessed by magnetic resonance and proctoscopy. The correlation between pre-treatmentSEPTIN9gene methylation ratio, tumor size, tumor stage and tumor response was analyzed.Results:39 patients with locally advanced rectal cancer were included. Pre-treatment SEPTIN9 gene methylation ratio (p= 0.033) and tumor size (p= 0.026), but not tumor stage, significantly correlated with tumor response to total neoadjuvant therapy. Pre-treatment SEPTIN9 gene methylation ratio also correlated with N stage (p= 0.040) and tumor size (p= 0.001), but not with T stage (p= 0.846).Conclusions:Pre-treatment SEPTIN9 gene methylation ratio correlates with tumor size and N stage and can predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer.
背景与目的:目前已有多种标志物被提出,但尚无可靠的治疗前标志物能够预测局部进展期直肠癌患者对全疗程新辅助治疗的肿瘤反应。本研究旨在评估治疗前SEPTIN9基因甲基化比率作为预测局部进展期直肠癌患者对全疗程新辅助治疗肿瘤反应的标志物的有效性,及其与肿瘤大小和肿瘤分期的相关性。 方法:研究纳入接受全疗程新辅助治疗的局部进展期直肠癌患者(经组织学确诊的T3/4期和/或淋巴结阳性直肠癌)。通过磁共振成像确定肿瘤大小和肿瘤分期。在诊断时采用微滴式数字PCR技术分析血浆游离DNA中SEPTIN9基因的甲基化状态。完成全疗程新辅助治疗后,通过磁共振成像和直肠镜评估肿瘤反应。分析治疗前SEPTIN9基因甲基化比率与肿瘤大小、肿瘤分期及肿瘤反应之间的相关性。 结果:共纳入39例局部进展期直肠癌患者。治疗前SEPTIN9基因甲基化比率(p=0.033)和肿瘤大小(p=0.026)与全疗程新辅助治疗的肿瘤反应显著相关,而肿瘤分期则无显著相关性。治疗前SEPTIN9基因甲基化比率还与N分期(p=0.040)和肿瘤大小(p=0.001)相关,但与T分期无关(p=0.846)。 结论:治疗前SEPTIN9基因甲基化比率与肿瘤大小和N分期相关,能够预测局部进展期直肠癌患者对全疗程新辅助治疗的肿瘤反应。