KRAS 和 GNAS 突变在游离DNA及循环上皮细胞中的检测及其在导管内乳头状黏液性肿瘤患者中的应用——一项观察性初步研究

KRAS and GNAS mutations in cell-free DNA and in circulating epithelial cells in patients with intraductal papillary mucinous neoplasms-an observational pilot study

Molecular Oncology

影响因子:4.5

分区:医学2区 / 肿瘤学3区

发表日期:2025 Jul

作者: Christine Nitschke, Marie Tölle, Philipp Walter, Kira Meißner, Mara Goetz, Jolanthe Kropidlowski, Andreas W Berger, Jakob R Izbicki, Felix Nickel, Thilo Hackert, Klaus Pantel, Harriet Wikman, Faik G Uzunoglu

DOI: 10.1002/1878-0261.13719

摘要

导管内乳头状黏液性肿瘤（IPMN）是胰腺癌的潜在前驱病变。我们评估了利用数字滴度聚合酶链反应（ddPCR）检测细胞游离DNA（cfDNA）中的KRAS原癌基因GTP酶（KRAS）和GNAS复合位点（GNAS）突变，以及循环上皮细胞（CEC）检测，作为风险分层的生物标志物的检测效果。我们前瞻性收集了25例有恶性进展风险的切除患者的血浆样本，以及23例接受临床监测的患者样本。我们的研究发现，整体队列中KRAS突变的检出率为10.4%，GNAS突变为18.8%。在切除的IPMN患者中，KRAS和GNAS突变的检出率分别为16.0%和32.0%，而在保守管理的IPMN中这两个比率均为4.0%。cfDNA中的GNAS突变在切除的IPMN中显著更为常见（P = 0.024）与正在监测的IPMN相比。未检测到CEC。KRAS和GNAS突变的缺失可能是没有令人担忧特征的分支导管IPMN的可靠标志。GNAS突变的出现可能提示加强影像监测。已确立的令人担忧特征的存在或GNAS或KRAS突变似乎都不能有效识别IPMN患者中的高级别异型增生。

Abstract

Intraductal papillary mucinous neoplasms (IPMNs) are potential precursor lesions of pancreatic cancer. We assessed the efficacy of screening for KRAS proto-oncogene, GTPase (KRAS), and GNAS complex locus (GNAS) mutations in cell-free DNA (cfDNA)-using digital droplet polymerase chain reaction (ddPCR) and circulating epithelial cell (CEC) detection-as biomarkers for risk stratification in IPMN patients. We prospectively collected plasma samples from 25 resected patients at risk of malignant progression, and 23 under clinical surveillance. Our findings revealed KRAS mutations in 10.4% and GNAS mutations in 18.8% of the overall cohort. Among resected IPMN patients, KRAS and GNAS mutation detection rates were 16.0% and 32.0%, respectively, whereas both rates were 4.0% in conservatively managed IPMN. GNAS mutations in cfDNA were significantly more prevalent in resected IPMN (P = 0.024) compared with IPMN under surveillance. No CECs were detected. The absence of KRAS and GNAS mutations could be a reliable marker for branch duct IPMN without worrisome features. The emergence of GNAS mutations could prompt enhanced imaging surveillance. Neither the presence of established worrisome features nor GNAS or KRAS mutations appear effective in identifying high-grade dysplasia among IPMN patients.