在 HUNT 研究中，在临床诊断结直肠癌之前检测到的循环肿瘤 DNA 的预后作用。
The prognostic role of circulating tumour DNA detected prior to clinical diagnosis of colorectal cancer in the HUNT study.
机构信息
Department of Surgery, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
Department of Public Health and Nursing, HUNT Research Centre, Norwegian University of Science and Technology, Levanger, Norway.
出版信息
BMC Cancer. 2024 Oct 10;24(1):1251. doi: 10.1186/s12885-024-13030-x.
BACKGROUND
Today, the prognostic tools available at the time of diagnosis in colorectal cancer (CRC) are limited. Better prognostic tools are a prerequisite for personalised treatment. This study aimed to investigate whether circulating tumour DNA (ctDNA) markers found in plasma before clinical diagnosis of CRC could contribute to the prediction of poor prognosis.
METHODS
This observational cohort study included patients diagnosed with CRC stage I-III within 24 months following participation in the Trøndelag Health Study (n = 85). Known methylated ctDNA biomarkers of CRC were analysed by PCR in plasma. Outcomes were overall survival (OS), recurrence-free survival (RFS) and poor prognosis (PP). Candidate clinical and methylated ctDNA predictors of the outcomes were identified by Cox regression analyses.
RESULTS
Methylated GRIA4 (HR 1.96 (1.06-3.63)), RARB (HR 9.48 (3.00-30.00)), SLC8A1 (HR 1.97 (1.03-3.77)), VIM (HR 2.95 (1.22-7.14)) and WNT5A (HR 5.83 (2.33-14.56)) were independent predictors of OS, methylated RARB (HR 9.67 (2.54-36.81)), SDC2 (HR 3.38 (1.07-10.66)), SLC8A1 (HR 2.93 (1.01-8.51)) and WNT5A (HR 6.95 (1.81-26.68)) were independent predictors of RFS and methylated RARB (HR 6.11 (1.69-22.18)), SDC2 (HR 2.79 (1.20-6.49)) and WNT5A (HR 5.57 (3.04-15.26)) were independent predictors of PP (p < 0.05).
CONCLUSIONS
Prediagnostic ctDNA markers are promising contributors to predicting poor prognosis in CRC, potentially becoming one of the tools guiding more personalised treatment.
背景
目前，结直肠癌（CRC）诊断时可用的预后工具有限。更好的预后工具是个性化治疗的前提。本研究旨在探讨 CRC 临床诊断前血浆中循环肿瘤 DNA（ctDNA）标志物是否有助于预测不良预后。
方法
本观察性队列研究纳入了在参加特隆赫姆健康研究后 24 个月内被诊断为 CRC I-III 期的患者（n=85）。采用 PCR 分析血浆中已知的 CRC 甲基化 ctDNA 生物标志物。结局为总生存期（OS）、无复发生存期（RFS）和不良预后（PP）。通过 Cox 回归分析确定结局的候选临床和甲基化 ctDNA 预测因子。
结果
甲基化 GRIA4（HR 1.96[1.06-3.63]）、RARB（HR 9.48[3.00-30.00]）、SLC8A1（HR 1.97[1.03-3.77]）、VIM（HR 2.95[1.22-7.14]）和 WNT5A（HR 5.83[2.33-14.56]）是 OS 的独立预测因子，甲基化 RARB（HR 9.67[2.54-36.81]）、SDC2（HR 3.38[1.07-10.66]）、SLC8A1（HR 2.93[1.01-8.51]）和 WNT5A（HR 6.95[1.81-26.68]）是 RFS 的独立预测因子，甲基化 RARB（HR 6.11[1.69-22.18]）、SDC2（HR 2.79[1.20-6.49]）和 WNT5A（HR 5.57[3.04-15.26]）是 PP 的独立预测因子（p<0.05）。
结论
预测性 ctDNA 标志物有望成为预测 CRC 不良预后的指标之一，有可能成为指导更个体化治疗的工具之一。
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