A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease.


RESULTS
We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7-10.0). Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group.


CONCLUSIONS
Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets. Please see later in the article for the Editors' Summary.
Stratford
Jeran K
JK
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Bentrem
David J
DJ
Anderson
Judy M
JM
Fan
Cheng
C
Volmar
Keith A
KA
Marron
J S
JS
Routh
Elizabeth D
ED
Caskey
Laura S
LS
Samuel
Jonathan C
JC
Der
Channing J
CJ
Thorne
Leigh B
LB
Calvo
Benjamin F
BF
Kim
Hong Jin
HJ
Talamonti
Mark S
MS
Iacobuzio-Donahue
Christine A
CA
Hollingsworth
Michael A
MA
Perou
Charles M
CM
Yeh
Jen Jen
JJ
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis