PMID- 27846146
DCOM- 20180306
LR  - 20180413
IS  - 1536-4828 (Electronic)
IS  - 0885-3177 (Linking)
VI  - 46
IP  - 3
DP  - 2017 Mar
TI  - Identification and Validation of Novel Subtype-Specific Protein Biomarkers in
      Pancreatic Ductal Adenocarcinoma.
PG  - 311-322
LID - 10.1097/MPA.0000000000000743 [doi]
AB  - OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) has been subclassified into 3
      molecular subtypes: classical, quasi-mesenchymal, and exocrine-like. These
      subtypes exhibit differences in patient survival and drug resistance to
      conventional therapies. The aim of the current study is to identify novel
      subtype-specific protein biomarkers facilitating subtype stratification of
      patients with PDAC and novel therapy development. METHODS: A set of 12 human
      patient-derived primary cell lines was used as a starting material for an
      advanced label-free proteomics approach leading to the identification of novel
      cell surface and secreted biomarkers. Cell surface protein identification was
      achieved by in vitro biotinylation, followed by mass spectrometric analysis of
      purified biotin-tagged proteins. Proteins secreted into a chemically defined
      serum-free cell culture medium were analyzed by shotgun proteomics. RESULTS: Of
      3288 identified proteins, 2 pan-PDAC (protocadherin-1 and lipocalin-2) and 2
      exocrine-like-specific (cadherin-17 and galectin-4) biomarker candidates have
      been validated. Proximity ligation assay analysis of the 2 exocrine-like
      biomarkers revealed their co-localization on the surface of exocrine-like cells. 
      CONCLUSIONS: The study reports the identification and validation of novel PDAC
      biomarkers relevant for the development of patient stratification tools. In
      addition, cadherin-17 and galectin-4 may serve as targets for bispecific
      antibodies as novel therapeutics in PDAC.
FAU - Kuhlmann, Laura
AU  - Kuhlmann L
AD  - From the *German Cancer Research Center (DKFZ), Heidelberg, Germany;
      daggerPrincess Margaret Cancer Center, Toronto, Ontario, Canada; double
      daggerHeidelberg Institute for Stem Cell Technology and Experimental Medicine
      (HI-STEM gGmbH), Heidelberg, Germany; and section signNovartis Pharma AG, Basel, 
FAU - Nadler, Wiebke M
AU  - Nadler WM
FAU - Kerner, Alexander
AU  - Kerner A
FAU - Hanke, Sabrina A
AU  - Hanke SA
FAU - Noll, Elisa M
AU  - Noll EM
FAU - Eisen, Christian
AU  - Eisen C
FAU - Espinet, Elisa
AU  - Espinet E
FAU - Vogel, Vanessa
AU  - Vogel V
FAU - Trumpp, Andreas
AU  - Trumpp A
FAU - Sprick, Martin R
AU  - Sprick MR
FAU - Roesli, Christoph P
AU  - Roesli CP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pancreas
JT  - Pancreas
JID - 8608542
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CDH17 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Galectin 4)
RN  - 0 (Lipocalin-2)
RN  - 0 (PCDH11X protein, human)
RN  - 0 (Proteome)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor/*metabolism
MH  - Cadherins/metabolism
MH  - Carcinoma, Pancreatic Ductal/diagnosis/*metabolism
MH  - Galectin 4/metabolism
MH  - Humans
MH  - Lipocalin-2/metabolism
MH  - Mice
MH  - Pancreatic Neoplasms/diagnosis/*metabolism
MH  - Proteome/*metabolism
MH  - Proteomics/*methods
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
MH  - Transplantation, Heterologous
EDAT- 2016/11/16 06:00
MHDA- 2018/03/07 06:00
CRDT- 2016/11/16 06:00
PHST- 2016/11/16 06:00 [pubmed]
PHST- 2018/03/07 06:00 [medline]
PHST- 2016/11/16 06:00 [entrez]
AID - 10.1097/MPA.0000000000000743 [doi]
PST - ppublish
SO  - Pancreas. 2017 Mar;46(3):311-322. doi: 10.1097/MPA.0000000000000743.