Journal of Cancer Research and Clinical Oncology

, Volume 141, Issue 2, pp 369–380 | Cite as

Protein deep sequencing applied to biobank samples from patients with pancreatic cancer

  • Daniel Ansari
  • Roland Andersson
  • Monika P. Bauden
  • Bodil Andersson
  • Joanne B. Connolly
  • Charlotte Welinder
  • Agata Sasor
  • György Marko-Varga
Original Article – Clinical Oncology

Abstract

Purpose

Pancreatic cancer is commonly detected at advanced stages when the tumor is no longer amenable to surgical resection. Therefore, finding biomarkers for early stage disease is urgent. Here, we show that high-definition mass spectrometry (HDMSE) can be used to identify serum protein alterations associated with early stage pancreatic cancer.

Methods

We analyzed serum samples from patients with resectable pancreatic cancer, benign pancreatic disease, and healthy controls. The SYNAPT G2-Si platform was used in a data-independent manner coupled with ion mobility. The dilution of the samples with yeast alcohol dehydrogenase tryptic digest of known concentration allowed the estimated amounts of each identified protein to be calculated (Silva et al. in Anal Chem 77:2187–2200, 2005; Silva et al. in Mol Cell Proteomics 5:144–156, 2006). A global protein expression comparison of the three study groups was made using label-free quantification and bioinformatic analyses.

Results

Two-way unsupervised hierarchical clustering revealed 134 proteins that successfully classified pancreatic cancer patients from the controls, and identified 40 proteins that showed a significant up-regulation in the pancreatic cancer group. This discrimination reliability was further confirmed by principal component analysis. The differentially expressed candidates were aligned with protein network analyses and linked to biological pathways related to pancreatic tumorigenesis. Pancreatic disease link associations could be made for BAZ2A, CDK13, DAPK1, DST, EXOSC3, INHBE, KAT2B, KIF20B, SMC1B, and SPAG5, by pathway network linkages to p53, the most frequently altered tumor suppressor in pancreatic cancer.

Conclusion

These pancreatic cancer study candidates may provide new avenues of research for a noninvasive blood-based diagnosis for pancreatic tumor stratification.

Keywords

Early detection High-definition mass spectrometry Ion mobility Pancreatic cancer Serum biomarkers 

Supplementary material

432_2014_1817_MOESM1_ESM.tif (1.4 mb)
Gene ontology classification of proteins identified in the serum samples (TIFF 1388 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Daniel Ansari
    • 1
  • Roland Andersson
    • 1
  • Monika P. Bauden
    • 1
  • Bodil Andersson
    • 1
  • Joanne B. Connolly
    • 2
  • Charlotte Welinder
    • 3
  • Agata Sasor
    • 4
  • György Marko-Varga
    • 3
  1. 1.Department of Surgery, Clinical Sciences LundLund University, Skåne University HospitalLundSweden
  2. 2.Waters CorporationManchesterUK
  3. 3.Clinical Protein Science and Imaging, Department of Measurement Technology and Industrial Electrical Engineering, Biomedical Center, BMC D13Lund UniversityLundSweden
  4. 4.Department of Pathology, Clinical Sciences LundLund University, Skåne University HospitalLundSweden

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