循环游离DNA与循环上皮细胞中KRAS和GNAS突变在胰腺导管内乳头状黏液性肿瘤患者中的观察性初步研究
KRAS and GNAS mutations in cell-free DNA and in circulating epithelial cells in patients with intraductal papillary mucinous neoplasms-an observational pilot study
影响因子:4.50000
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
摘要
胰腺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PCR（ddPCR）检测循环游离DNA（cfDNA）和循环上皮细胞（CEC）中的KRAS原癌基因（KRAS）和GNAS复合位点（GNAS）突变作为IPMN患者风险分层的生物标志物的有效性。我们前瞻性收集了25例有恶变风险且已切除的患者及23例在临床监测中的患者的血浆样本。研究发现，整体队列中KRAS突变比例为10.4%，GNAS突变比例为18.8%。在手术切除的IPMN患者中，KRAS和GNAS突变的检出率分别为16.0%和32.0%；而在保守治疗的IPMN中，两者检出率均为4.0%。GNAS突变在cfDNA中的检出在切除患者中显著高于监测患者（P=0.024）。未检测到循环上皮细胞。未检测到KRAS和GNAS突变可能是无危险特征的分支管IPMN的可靠标志，而GNAS突变的出现可能提示需要加强影像监测。目前，既往存在的危险特征及GNAS或KRAS突变在识别高等级不典型增生（高风险）方面的效果有限。
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.