% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Werner:186672,
      author       = {J. Werner and P. Bernhard and M. Cosenza-Contreras and N.
                      Pinter and M. Fahrner$^*$ and P. Pallavi and J. Eberhard and
                      P. Bronsert and F. Rückert and O. Schilling$^*$},
      title        = {{T}argeted and explorative profiling of kallikrein
                      proteases and global proteome biology of pancreatic ductal
                      adenocarcinoma, chronic pancreatitis, and normal pancreas
                      highlights disease-specific proteome remodelling.},
      journal      = {Neoplasia},
      volume       = {36},
      issn         = {1522-8002},
      address      = {Basingstoke},
      publisher    = {Stockton Press},
      reportid     = {DKFZ-2023-00041},
      pages        = {100871},
      year         = {2023},
      abstract     = {Pancreatic ductal adenocarcinoma (PDAC) represents one of
                      the most aggressive and lethal malignancies worldwide with
                      an urgent need for new diagnostic and therapeutic
                      strategies. One major risk factor for PDAC is the
                      pre-indication of chronic pancreatitis (CP), which
                      represents highly inflammatory pancreatic tissue.
                      Kallikreins (KLKs) are secreted serine proteases that play
                      an important role in various cancers as components of the
                      tumor microenvironment. Previous studies of KLKs in solid
                      tumors largely relied on either transcriptomics or
                      immunodetection. We present one of the first targeted mass
                      spectrometry profiling of kallikrein proteases in PDAC, CP,
                      and normal pancreas. We show that KLK6 and KLK10 are
                      significantly upregulated in PDAC (n=14) but not in CP (n=7)
                      when compared to normal pancreas (n=16), highlighting their
                      specific intertwining with malignancy. Additional
                      explorative proteome profiling identified 5936 proteins in
                      our pancreatic cohort and observed disease-specific proteome
                      rearrangements in PDAC and CP. As such, PDAC features an
                      enriched proteome motif for extracellular matrix (ECM) and
                      cell adhesion while there is depletion of mitochondrial
                      energy metabolism proteins, reminiscent of the Warburg
                      effect. Although often regarded as a PDAC hallmark, the ECM
                      fingerprint was also observed in CP, alongside with a
                      prototypical inflammatory proteome motif as well as with an
                      increased wound healing process and proteolytic activity,
                      thereby possibly illustrating tissue autolysis.
                      Proteogenomic analysis based on publicly accessible data
                      sources identified 112 PDAC-specific and 32 CP-specific
                      single amino acid variants, which among others affect KRAS
                      and ANKHD1. Our study emphasizes the diagnostic potential of
                      kallikreins and provides novel insights into proteomic
                      characteristics of PDAC and CP.},
      keywords     = {FFPE (Other) / KLK (Other) / Mass Spectrometry (Other) /
                      PDAC (Other)},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36610378},
      doi          = {10.1016/j.neo.2022.100871},
      url          = {https://inrepo02.dkfz.de/record/186672},
}