KRAS突变在多发性结直肠肿瘤中的预测作用：多发性息肉中的伴发突变分析

Prediction of metachronous advanced colorectal neoplasia by KRAS mutation in polyps

United European Gastroenterology Journal

影响因子:6.7

分区:医学2区 / 胃肠肝病学3区

发表日期:2024 Nov

作者: Alejandro Martínez-Roca, Joaquín Cubiella, Anabel García-Heredia, David Guill-Berbegal, Sandra Baile-Maxía, Carolina Mangas-Sanjuán, Noelia Sala-Miquel, Lucía Madero-Velazquez, Cristina Alenda, Pedro Zapater, Clara González-Núñez, Agueda Iglesias-Gómez, Laura Codesido-Prado, Astrid Díez-Martín, Michal F Kaminski, Rune Erichsen, Hans-Olov Adami, Monika Ferlitsch, María Pellisé, Øyvind Holme, Evelien Dekker, Michael Bretthauer, Rodrigo Jover,

DOI: 10.1002/ueg2.12667

摘要

在高风险腺瘤患者中，分子标志物作为预测多发性病变的可靠指标的潜力仍不确定。我们的目标是评估KRAS体细胞突变在高风险腺瘤患者多发性息肉中的作用，以预测三年内发生的高级病变或结直肠癌（CRC）。共招募518名患者，符合腺瘤≥10 mm、高级异型性、绒毛成分或≥3个腺瘤的入选标准，并计划在3年±6个月内进行随访结肠镜检查。对这些患者采集的1189个息肉进行了KRAS突变检测。随访时，定义为≥10 mm的腺瘤为高级病变，包括高等级异型性、绒毛成分、≥10 mm的锯齿状息肉、异型性或CRC。在基线时，81名患者（15.6%）在至少一个息肉中检测到KRAS突变。KRAS突变的息肉与更常见的绒毛组织学变化及≥20 mm的尺寸相关。在多变量分析中，调整年龄和性别后，年龄（比值比[OR] 1.06，95%置信区间[CI] 1.02-1.09，p<0.001）、≥5个腺瘤（OR 3.92，95% CI 1.96-7.82）以及KRAS突变（OR 2.54，95% CI 1.48-4.34，p<0.01）与随访中高级病变的发生显著相关。我们的研究显示，在高风险腺瘤患者中，KRAS的体细胞突变是高级异型性多发性息肉发生的独立风险因素。

Abstract

The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain.Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years.A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10 mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3 years ± 6 months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10 mm. High-grade dysplasia or villous component, serrated polyps ≥10 mm or with dysplasia or CRC.At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20 mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p < 0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p < 0.01) were independently associated with the development of advanced lesions at surveillance.Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.