title: Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma.
abstract: The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC) are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment decision-making process. To derive a prognostic gene signature for patients with early stage PDAC, a PDAC cohort from Moffitt Cancer Center (n = 63) was used with overall survival (OS) as the primary endpoint. This was further evaluated using an independent microarray cohort dataset (Stratford et al: n = 102). Technical validation was performed by NanoString platform. A prognostic 15-gene signature was developed and showed a statistically significant association with OS in the Moffitt cohort (hazard ratio [HR] = 3.26; p<0.001) and Stratford et al cohort (HR = 2.07; p = 0.02), and was independent of other prognostic variables. Moreover, integration of the signature with the TNM staging system improved risk prediction (p<0.01 in both cohorts). In addition, NanoString validation showed that the signature was robust with a high degree of reproducibility and the association with OS remained significant in the two cohorts. The gene signature could be a potential prognostic tool to allow risk-adapted stratification of PDAC patients into personalized treatment protocols; possibly improving the currently poor clinical outcomes of these patients.
authors.affiliation: Department of Biostatistics and Bioinformatics, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, United States of America.
authors.forename: Dung-Tsa
authors.initials: DT
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, United States of America.
authors.forename: Ashley H
authors.initials: AH
authors.lastname: Davis-Yadley
authors.affiliation: Department of Applied Mathematics and Institute of Statistics, National Chung Hsing University, Taichung City, Taiwan.
authors.forename: Po-Yu
authors.initials: PY
authors.lastname: Huang
authors.affiliation: Department of Gastrointestinal Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, United States of America.
authors.forename: Kazim
authors.initials: K
authors.lastname: Husain
authors.affiliation: Department of Anatomic Pathology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, United States of America.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Centeno
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Permuth-Wey
authors.affiliation: Department of Gastrointestinal Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, United States of America.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Pimiento
authors.affiliation: Department of Gastrointestinal Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, United States of America.
authors.forename: Mokenge
authors.initials: M
authors.lastname: Malafa
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D016019:Survival Analysis; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor