Protein biomarkers and alternatively methylated cell-free DNA detect early stage pancreatic cancer.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ben-Ami Roni, Wang Qiao-Li, Zhang Jinming, Supplee Julianna G, Fahrmann Johannes F, Lehmann-Werman Roni, Brais Lauren K, Nowak Jonathan, Yuan Chen, Loftus Maureen, Babic Ana, Irajizad Ehsan, Davidi Tal, Zick Aviad, Hubert Ayala, Neiman Daniel, Piyanzin Sheina, Gal-Rosenberg Ofer, Horn Amit, Shemer Ruth, Glaser Benjamin, Boos Natalia, Jajoo Kunal, Lee Linda, Clancy Thomas E, Rubinson Douglas A, Ng Kimmie, Chabot John A, Kastrinos Fay, Kluger Michael, Aguirre Andrew J, Jänne Pasi A, Bardeesy Nabeel, Stanger Ben, O'Hara Mark H, Till Jacob, Maitra Anirban, Carpenter Erica L, Bullock Andrea J, Genkinger Jeanine, Hanash Samir M, Paweletz Cloud P, Dor Yuval, Wolpin Brian M
Аннотация
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.