Fax: (919) 684-7168
Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303)
Article first published online: 28 JUN 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 2, pages 571–578, 15 January 2012
How to Cite
Roberts, A. S., Campa, M. J., Gottlin, E. B., Jiang, C., Owzar, K., Kindler, H. L., Venook, A. P., Goldberg, R. M., O'Reilly, E. M. and Patz, E. F. (2012), Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303). Cancer, 118: 571–578. doi: 10.1002/cncr.26270
- Issue published online: 5 JAN 2012
- Article first published online: 28 JUN 2011
- Manuscript Accepted: 13 APR 2011
- Manuscript Revised: 5 APR 2011
- Manuscript Received: 15 MAR 2011
- pancreatic neoplasms;
- biological markers;
- alpha 1-antichymotrypsin
Patients with advanced stage adenocarcinoma of the pancreas have a poor prognosis. The identification of prognostic and/or predictive biomarkers may help stratify patients so that therapy can be individualized.
Serum samples from patients enrolled in the Cancer and Leukemia Group B 80303 phase 3 trial, “Randomized Study of Gemcitabine With Versus Without Bevacizumab in Patients With Locally Advanced or Metastatic Adenocarcinoma of the Pancreas” were used to discover novel biomarkers. For the discovery phase, 40 sera were selected based on length of survival and type of therapy, and subjected to liquid chromatography coupled to tandem mass spectrometry analysis (LC-MS-MS). The top features (proteins) were then further selected for validation by enzyme-linked immunosorbent assay (ELISA).
Quantification by nano–LC-MS-MS resulted in 1452 peptides mapping to 156 proteins across all 40 samples, 92 of which had 2 or more peptides. After curation of the data, the authors selected 1 putative prognostic protein, alpha 1-antichymotrypsin (AACT), and 2 putative predictive proteins, histidine-rich glycoprotein (HRG) and complement factor H (CFH), for validation by ELISA. AACT was found to be negatively correlated with overall survival (τ = −0.30 [−0.38, −0.22]; P < .00001). There was no evidence for interaction with bevacizumab and HRG, but there was some evidence for a weak positive correlation of HRG with overall survival (τ = 0.11 [0.03, 0.19]; P < .01). CFH was found to be neither a predictive nor a prognostic factor for overall survival.
AACT may be a useful prognostic marker in patients with advanced stage pancreatic carcinoma, although additional validation studies are needed. Cancer 2011;. © 2011 American Cancer Society.