{Reference Type}: Journal Article
{Title}: Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer.
{Author}: Ben-Ami R;Wang QL;Zhang J;Supplee JG;Fahrmann JF;Lehmann-Werman R;Brais LK;Nowak J;Yuan C;Loftus M;Babic A;Irajizad E;Davidi T;Zick A;Hubert A;Neiman D;Piyanzin S;Gal-Rosenberg O;Horn A;Shemer R;Glaser B;Boos N;Jajoo K;Lee L;Clancy TE;Rubinson DA;Ng K;Chabot JA;Kastrinos F;Kluger M;Aguirre AJ;Jänne PA;Bardeesy N;Stanger B;O'Hara MH;Till J;Maitra A;Carpenter EL;Bullock AJ;Genkinger J;Hanash SM;Paweletz CP;Dor Y;Wolpin BM;
{Journal}: Gut
{Volume}: 73
{Issue}: 4
{Year}: 2024 03 7
{Factor}: 31.793
{DOI}: 10.1136/gutjnl-2023-331074
{Abstract}: 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.<BR>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.<BR>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).<BR>A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.