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Br J Cancer. 2015 Dec 1;113(11):1590-8. doi: 10.1038/bjc.2015.370. Epub 2015 Oct 29.

Pancreatic preneoplastic lesions plasma signatures and biomarkers based on proteome profiling of mouse models.

Author information

1
Proteomics Group, Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.
2
EA 4552, Université Toulouse III-Paul Sabatier, Toulouse 31432, France.
3
INSERM-US006 ANEXPLO/CREFRE-Histology facility, Toulouse 31024, France.
4
Centre de Recherches en Cancérologie de Marseille (CRCM), Inserm U1068, Institut Paoli-Calmettes, Université Aix-Marseille, CNRS, UMR7258, Marseille 13288, France.
5
Institut de Mathématiques de Toulouse, UMR 5219 CNRS, Université Toulouse III-Paul Sabatier, Toulouse 31062, France.
6
Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Equipe Labellisée Ligue Contre le Cancer, Toulouse 31037, France.
7
Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM UMR1037, Université Toulouse III-Paul Sabatier, Toulouse 31037, France.

Abstract

BACKGROUND:

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a mortality that is almost identical to incidence. Because early detected PDAC is potentially curable, blood-based biomarkers that could detect currently developing neoplasia would improve patient survival and management. PDAC develops from pancreatic intraepithelial neoplasia (PanIN) lesions, graded from low grade (PanIN1) to high grade (PanIN3). We made the hypothesis that specific proteomic signatures from each precancerous stage exist and are detectable in plasma.

METHODS:

We explored the peptide profiles of microdissected PanIN cells and of plasma samples corresponding to the different PanIN grade from genetically engineered mouse models of PDAC using capillary electrophoresis coupled to mass spectrometry (CE-MS) and Chip-MS/MS.

RESULTS:

We successfully characterised differential peptides profiles from PanIN microdissected cells. We found that plasma from tumor-bearing mice and age-matched controls exhibit discriminative peptide signatures. We also determined plasma peptide signatures corresponding to low- and high-grade precancerous step present in the mice pancreas using the two mass spectrometry technologies. Importantly, we identified biomarkers specific of PanIN3.

CONCLUSIONS:

We demonstrate that benign and advanced PanIN lesions display distinct plasma peptide patterns. This strongly supports the perspectives of developing a non-invasive screening test for prediction and early detection of PDAC.

PMID:
26512875
PMCID:
PMC4705884
DOI:
10.1038/bjc.2015.370
[Indexed for MEDLINE]
Free PMC Article

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