title: Commonality and differences of methylation signatures in the plasma of patients with pancreatic cancer and colorectal cancer.
abstract: Profiling of DNA methylation status of specific genes is a way to screen for colorectal cancer (CRC) and pancreatic cancer (PC) in blood. The commonality of methylation status of cancer-related tumor suppressor genes between CRC and PC is largely unknown. Methylation status of 56 cancer-related genes was compared in plasma of patients in the following cohorts: CRC, PC and healthy controls. Cross validation determined the best model by area under ROC curve (AUC) to differentiate cancer methylation profiles from controls. Optimal preferential gene methylation signatures were derived to differentiate either cancer (CRC or PC) from controls. For CRC alone, a three gene signature (CYCD2, HIC and VHL) had an AUC 0.9310, sensitivity (Sens) = 0.826, specificity (Spec) = 0.9383. For PC alone, an optimal signature consisted of five genes (VHL, MYF3, TMS, GPC3 and SRBC), AUC 0.848; Sens = 0.807, Spec = 0.666. Combined PC and CRC signature or "combined cancer signature" was derived to differentiate either CRC and PC from controls (MDR1, SRBC, VHL, MUC2, RB1, SYK and GPC3) AUC = 0.8177, Sens = 0.6316 Spec = 0.840. In a validation cohort, N = 10 CRC patients, the optimal CRC signature (CYCD2, HIC and VHL) had AUC 0.900. In all derived signatures (CRC, PC and combined cancer signature) the optimal panel used preferential VHL methylation. In conclusion, CRC and PC differ in specific genes methylated in plasma other than VHL. Preferential methylation of VHL is shared in the optimal signature for CRC alone, PC alone and combined PC and CRC. Future investigations may identify additional methylation markers informative for the presence of both CRC and PC.
authors.affiliation: Division of Digestive Diseases, Rush University Medical Center, Chicago, IL.
authors.forename: Joshua
authors.initials: J
authors.lastname: Melson
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Elisa
authors.initials: E
authors.lastname: Cassinotti
authors.forename: Anatoliy
authors.initials: A
authors.lastname: Melnikov
authors.forename: Luigi
authors.initials: L
authors.lastname: Boni
authors.forename: Junmei
authors.initials: J
authors.lastname: Ai
authors.forename: Michael
authors.initials: M
authors.lastname: Greenspan
authors.forename: Sohrab
authors.initials: S
authors.lastname: Mobarhan
authors.forename: Victor
authors.initials: V
authors.lastname: Levenson
authors.forename: Youping
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarkers; cancer screening; colorectal cancer; epigenetics; methylation; pancreatic cancer