Jen Jen Yeh and colleagues developed and validated a six-gene signature in patients with pancreatic ductal adenocarcinoma that may be used to better stage the disease in these patients and assist in treatment decisions

Anderson, Judy M.

Bentrem, David J.

Calvo, Benjamin F.

Caskey, Laura S.

Der, Channing J.

Fan, Cheng

Hollingsworth, Michael A.

Iacobuzio-Donahue, Christine A.

Kim, Hong Jin

Marron, J. S.

Perou, Charles M.

Routh, Elizabeth D.

Samuel, Jonathan C.

Stratford, Jeran K.

Talamonti, Mark S.

Thorne, Leigh B.

Volmar, Keith A.

Yeh, Jen Jen

PLoS Medicine

English

PubMed

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.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.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' Summar

Stratford Jeran K.

Bentrem David J.

Anderson Judy M.

Fan Cheng

Volmar Keith A.

Marron J. S.

Routh Elizabeth D.

Caskey Laura S.

Samuel Jonathan C.

Der Channing J.

Thorne Leigh B.

Calvo Benjamin F.

Kim Hong Jin

Talamonti Mark S.

Iacobuzio-Donahue Christine A.

Hollingsworth Michael A.

Perou Charles M.

Yeh Jen Jen

Public Library of Science (PLOS)

A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma

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.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.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

Jeran K Stratford

David J Bentrem

Judy M Anderson

Cheng Fan

Keith A Volmar

J S Marron

Elizabeth D Routh

Laura S Caskey

Jonathan C Samuel

Channing J Der

Leigh B Thorne

Benjamin F Calvo

Hong Jin Kim

Mark S Talamonti

Christine A Iacobuzio-Donahue

Michael A Hollingsworth

Charles M Perou

Jen Jen Yeh

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A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma

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