Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer

医学 阶段(地层学) 胰腺癌 甲基化 内科学 DNA甲基化 胰腺 接收机工作特性 胎儿游离DNA 胃肠病学 液体活检 胰腺炎,慢性 生物标志物 CpG站点 肿瘤科 曲线下面积 胰腺炎 癌症 结直肠癌 生物 基因 基因表达 遗传学 怀孕 产前诊断 胎儿 古生物学
作者
Roni Ben‐Ami,Qiao-Li Wang,Jinming Zhang,Julianna Supplee,Johannes F. Fahrmann,Roni Lehmann‐Werman,Lauren K. Brais,Jonathan A. Nowak,Chen Yuan,Maureen Loftus,Ana Babić,Ehsan Irajizad,Tal Davidi,Aviad Zick,Ayala Hubert,Daniel Neiman,Sheina Piyanzin,Ofer Gal-Rosenberg,Amit Horn,Ruth Shemer,Benjamin Gläser,Natalia Boos,Kunal Jajoo,Linda Lee,Thomas E. Clancy,Douglas A. Rubinson,Kimmie Ng,John A. Chabot,Fay Kastrinos,Michael D. Kluger,Andrew J. Aguirre,Pasi A. Jänne,Nabeel Bardeesy,Ben Z. Stanger,Mark H. O’Hara,Jacob E. Till,Anirban Maitra,Erica L. Carpenter,Andrea J. Bullock,Jeanine M. Genkinger,Samir Hanash,Cloud P. Paweletz,Yuval Dor,Brian M. Wolpin
出处
期刊:Gut [BMJ]
卷期号:: gutjnl-331074 被引量:12
标识
DOI:10.1136/gutjnl-2023-331074
摘要

Objective Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed. Design To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites. Results Comparative methylome analysis identified nine loci that were differentially methylated in exocrine pancreas DNA. In the training set (n=124 patients), cfDNA methylation markers distinguished PDAC from healthy and CRC controls. In the testing set of 86 early stage PDAC and 86 matched healthy controls, CA19-9 had an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI 0.83 to 0.94), which was increased by adding TIMP1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.06), LRG1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02) or exocrine pancreas-specific cfDNA methylation markers at nine loci (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02). In the validation set of 40 early stage PDAC and 40 matched healthy controls, a combined panel including CA19-9, TIMP1 and a 9-loci cfDNA methylation panel had greater discrimination (AUC 0.86, 95% CI 0.77 to 0.95) than CA19-9 alone (AUC 0.82; 95% CI 0.72 to 0.92). Conclusion A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.
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