A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma

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

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

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. Methods and Findings: 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.

Original languageEnglish (US)
JournalPLoS medicine
Volume7
Issue number7
DOIs
StatePublished - Jul 1 2010

Fingerprint

Adenocarcinoma
Survival
Genes
Neoplasms
Neoadjuvant Therapy
Transcriptome
Survival Rate
Biomarkers
Clinical Trials
Confidence Intervals
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Stratford, J. K., Bentrem, D. J., Anderson, J. M., Fan, C., Volmar, K. A., Marron, J. S., ... Yeh, J. J. (2010). A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma. PLoS medicine, 7(7). https://doi.org/10.1371/journal.pmed.1000307

A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma. / 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.

In: PLoS medicine, Vol. 7, No. 7, 01.07.2010.

Research output: Contribution to journalArticle

Stratford, JK, Bentrem, DJ, Anderson, JM, Fan, C, Volmar, KA, Marron, JS, Routh, ED, Caskey, LS, Samuel, JC, Der, CJ, Thorne, LB, Calvo, BF, Kim, HJ, Talamonti, MS, Iacobuzio-Donahue, CA, Hollingsworth, MA, Perou, CM & Yeh, JJ 2010, 'A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma', PLoS medicine, vol. 7, no. 7. https://doi.org/10.1371/journal.pmed.1000307
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. / A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma. In: PLoS medicine. 2010 ; Vol. 7, No. 7.
@article{c34cd9f7868d48db86796888f6412261,
title = "A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma",
abstract = "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. Methods and Findings: 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.",
author = "Stratford, {Jeran K.} and Bentrem, {David J.} and Anderson, {Judy M.} and Cheng Fan and Volmar, {Keith A.} and Marron, {J. S.} and Routh, {Elizabeth D.} and Caskey, {Laura S.} and Samuel, {Jonathan C.} and Der, {Channing J.} and Thorne, {Leigh B.} and Calvo, {Benjamin F.} and Kim, {Hong Jin} and Talamonti, {Mark S.} and Iacobuzio-Donahue, {Christine A.} and Hollingsworth, {Michael A} and Perou, {Charles M.} and Yeh, {Jen Jen}",
year = "2010",
month = "7",
day = "1",
doi = "10.1371/journal.pmed.1000307",
language = "English (US)",
volume = "7",
journal = "PLoS Medicine",
issn = "1549-1277",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma

AU - Stratford, Jeran K.

AU - Bentrem, David J.

AU - Anderson, Judy M.

AU - Fan, Cheng

AU - Volmar, Keith A.

AU - Marron, J. S.

AU - Routh, Elizabeth D.

AU - Caskey, Laura S.

AU - Samuel, Jonathan C.

AU - Der, Channing J.

AU - Thorne, Leigh B.

AU - Calvo, Benjamin F.

AU - Kim, Hong Jin

AU - Talamonti, Mark S.

AU - Iacobuzio-Donahue, Christine A.

AU - Hollingsworth, Michael A

AU - Perou, Charles M.

AU - Yeh, Jen Jen

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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. Methods and Findings: 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.

AB - 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. Methods and Findings: 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.

UR - http://www.scopus.com/inward/record.url?scp=77955048480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955048480&partnerID=8YFLogxK

U2 - 10.1371/journal.pmed.1000307

DO - 10.1371/journal.pmed.1000307

M3 - Article

VL - 7

JO - PLoS Medicine

JF - PLoS Medicine

SN - 1549-1277

IS - 7

ER -