循环肿瘤DNA和粪便免疫化学检测在双检测结直肠癌筛查中的应用。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer Pub Date : 2025-03-19 DOI:10.1016/j.clcc.2025.03.001

Caroline L. Kahn , Mathias M. Petersen , Jakob Kleif , Mees S.E. Mansvelders , Morten Rasmussen , Lars N. Jørgensen , Jesper Vilandt , Jakob B. Seidelin , Claudia Jaensch , Peter Bondeven , Kåre A. Gotschalck , Uffe S. Løve , Berit Andersen , Ib J. Christensen , Lawrence C. LaPoint , Christina Therkildsen

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引用次数: 0

摘要

背景：早期发现对于降低结直肠癌（CRC）的发病率和死亡率至关重要。目前基于人群的筛查计划主要使用粪便免疫化学试验（FIT）来分配个体进行结肠镜检查，尽管低特异性挑战结肠镜检查能力。我们的目的是评估循环肿瘤（ct）DNA标记在FIT阳性个体的双重CRC筛查方法中早期CRC检测的潜力。方法：分析来自丹麦CRC筛查项目的774例FIT阳性（≥100 ng血红蛋白/mL）个体的血浆样本，检测支链氨基酸转氨酶1 （BCAT1）、ikarros家族锌指转录1 （IKZF1）和干扰素调节因子4 （IRF4）基因的高甲基化DNA。将ctDNA标记物和年龄加入FIT值，建立多元logistic回归模型。双检验方法在特定阈值上对FIT进行基准测试。结果：与单独使用FIT相比，双重检测方法提高了CRC的检出率（AUC为87.2 [95% CI, 82.9-91.4]， AUC为72.5 [95% CI, 67.0-77.9]）。当在结果中加入晚期腺瘤时也可以看到这一点，双检验方法的auc为71.8 [95% CI, 67.8-75.8]，而单独使用FIT模型的auc为65.5 [95% CI, 61.3-69.7]。对FIT截止值在100 - 600 ng Hb/mL之间的双重测试方法进行基准测试显示，可能将结肠镜检查要求降低高达56%，或将CRC检测提高高达28%。结论：提高FIT临界值会降低结直肠癌的检出率，ctDNA检测在无症状人群中可以提高双重检测的敏感性和特异性。

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Circulating Tumor DNA in Addition to Fecal Immunochemical Test in a Dual-Test Colorectal Cancer Screening Approach

Background

Early detection is paramount when reducing incidence and mortality of colorectal cancer (CRC). Current population-based screening programs primarily use fecal immunochemical test (FIT) to allocate individuals for colonoscopy although low specificity challenges colonoscopy capacities. We aimed to assess the potential of circulating tumor (ct)DNA markers for early CRC detection in a dual-test CRC screening approach among FIT positive individuals.

Methods

Plasma samples from 774 FIT positive (≥100 ng Hemoglobin/mL) individuals from the Danish CRC screening program were analyzed for hypermethylated DNA in the genes Branched Chain Amino-acid Transaminase 1 (BCAT1), Ikaros-Family Zinc Finger transcription 1 (IKZF1), and Interferon Regulator Factor 4 (IRF4). Multivariate logistic regression models were generated adding the ctDNA markers and age to the FIT value. The dual-test approach was benchmarked to FIT at specific thresholds.

Results

The dual-test approach improved CRC detection compared to the FIT alone (AUC of 87.2 [95% CI, 82.9-91.4] vs AUC of 72.5 [95% CI, 67.0-77.9]). This was also seen when adding advanced adenomas to the outcome resulting in AUCs of 71.8 [95% CI, 67.8-75.8] for the dual-test approach compared to 65.5 [95% CI, 61.3-69.7] for the FIT model alone. Benchmarking the dual-test approach at FIT cut-offs between 100 and 600 ng Hb/mL showed a potential for either reducing the colonoscopy requirement by up to 56% or increasing CRC detection by up to 28%.

Conclusions

As increasing FIT cutoff will decrease CRC detection rate, application of the ctDNA panel can increase the sensitivity and specificity in a dual-test approach among asymptomatic individuals.

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来源期刊

Clinical colorectal cancer 医学-肿瘤学

CiteScore

5.50

自引率

2.90%

发文量

审稿时长

27 days

期刊介绍： Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.