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Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303).

Publication ,  Journal Article
Roberts, AS; Campa, MJ; Gottlin, EB; Jiang, C; Owzar, K; Kindler, HL; Venook, AP; Goldberg, RM; O'Reilly, EM; Patz, EF
Published in: Cancer
January 15, 2012

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: AACT may be a useful prognostic marker in patients with advanced stage pancreatic carcinoma, although additional validation studies are needed.

Duke Scholars

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Published In

Cancer

DOI

EISSN

1097-0142

Publication Date

January 15, 2012

Volume

118

Issue

2

Start / End Page

571 / 578

Location

United States

Related Subject Headings

  • alpha 1-Antichymotrypsin
  • Prognosis
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • Female
  • Clinical Trials, Phase III as Topic
  • Biomarkers, Tumor
 

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Roberts, A. S., Campa, M. J., Gottlin, E. B., Jiang, C., Owzar, K., Kindler, H. L., … 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(2), 571–578. https://doi.org/10.1002/cncr.26270
Roberts, Andrew S., Michael J. Campa, Elizabeth B. Gottlin, Chen Jiang, Kouros Owzar, Hedy L. Kindler, Alan P. Venook, Richard M. Goldberg, Eileen M. O’Reilly, and Edward F. Patz. “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, no. 2 (January 15, 2012): 571–78. https://doi.org/10.1002/cncr.26270.
Roberts, Andrew S., et al. “Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303).Cancer, vol. 118, no. 2, Jan. 2012, pp. 571–78. Pubmed, doi:10.1002/cncr.26270.
Roberts AS, Campa MJ, Gottlin EB, Jiang C, Owzar K, Kindler HL, Venook AP, Goldberg RM, O’Reilly EM, Patz EF. Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303). Cancer. 2012 Jan 15;118(2):571–578.
Journal cover image

Published In

Cancer

DOI

EISSN

1097-0142

Publication Date

January 15, 2012

Volume

118

Issue

2

Start / End Page

571 / 578

Location

United States

Related Subject Headings

  • alpha 1-Antichymotrypsin
  • Prognosis
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • Female
  • Clinical Trials, Phase III as Topic
  • Biomarkers, Tumor