A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest.
Currently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.Affymetrix gene expression profiling was carried out on 15 human PDAC tumors and from th...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4152146?pdf=render |
| _version_ | 1819100771738714112 |
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| author | Timothy E Newhook Edik M Blais James M Lindberg Sara J Adair Wenjun Xin Jae K Lee Jason A Papin J Thomas Parsons Todd W Bauer |
| author_facet | Timothy E Newhook Edik M Blais James M Lindberg Sara J Adair Wenjun Xin Jae K Lee Jason A Papin J Thomas Parsons Todd W Bauer |
| author_sort | Timothy E Newhook |
| collection | DOAJ |
| description | Currently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.Affymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic cancer. Patients with high-risk scores had significantly higher risk of death compared to patients with low-risk scores (HR 2.27, p = 0.002). When the 13-gene score was combined with lymph node status the risk-score further discriminated the length of patient survival time (p<0.001). Patients with a high-risk score had poor survival independent of nodal status; however, nodal status increased predictability for survival in patients with a low-risk gene signature score (low-risk N1 vs. low-risk N0: HR = 2.0, p = 0.002). While AJCC stage correlated with patient survival (p = 0.03), the 13-gene score was superior at predicting survival. Of the 13 genes comprising the predictive model, four have been shown to be important in PDAC, six are unreported in PDAC but important in other cancers, and three are unreported in any cancer.We identified a 13-gene expression signature that predicts survival of PDAC patients and could prove useful for making treatment decisions. This risk score should be evaluated prospectively in clinical trials for prognostication and for predicting response to chemotherapy. Investigation of new genes identified in our model may lead to novel therapeutic targets. |
| first_indexed | 2024-12-22T01:08:04Z |
| format | Article |
| id | doaj.art-bd1e56f5edfe469eb69c4306e672b877 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T01:08:04Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bd1e56f5edfe469eb69c4306e672b8772022-12-21T18:44:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10563110.1371/journal.pone.0105631A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest.Timothy E NewhookEdik M BlaisJames M LindbergSara J AdairWenjun XinJae K LeeJason A PapinJ Thomas ParsonsTodd W BauerCurrently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.Affymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic cancer. Patients with high-risk scores had significantly higher risk of death compared to patients with low-risk scores (HR 2.27, p = 0.002). When the 13-gene score was combined with lymph node status the risk-score further discriminated the length of patient survival time (p<0.001). Patients with a high-risk score had poor survival independent of nodal status; however, nodal status increased predictability for survival in patients with a low-risk gene signature score (low-risk N1 vs. low-risk N0: HR = 2.0, p = 0.002). While AJCC stage correlated with patient survival (p = 0.03), the 13-gene score was superior at predicting survival. Of the 13 genes comprising the predictive model, four have been shown to be important in PDAC, six are unreported in PDAC but important in other cancers, and three are unreported in any cancer.We identified a 13-gene expression signature that predicts survival of PDAC patients and could prove useful for making treatment decisions. This risk score should be evaluated prospectively in clinical trials for prognostication and for predicting response to chemotherapy. Investigation of new genes identified in our model may lead to novel therapeutic targets.http://europepmc.org/articles/PMC4152146?pdf=render |
| spellingShingle | Timothy E Newhook Edik M Blais James M Lindberg Sara J Adair Wenjun Xin Jae K Lee Jason A Papin J Thomas Parsons Todd W Bauer A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest. PLoS ONE |
| title | A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest. |
| title_full | A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest. |
| title_fullStr | A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest. |
| title_full_unstemmed | A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest. |
| title_short | A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest. |
| title_sort | thirteen gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest |
| url | http://europepmc.org/articles/PMC4152146?pdf=render |
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