Advanced

Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma

Hu, Dingyuan LU ; Ansari, Daniel LU ; Pawlowski, Krzysztof LU ; Zhou, Qimin LU ; Sasor, Agata; Welinder, Charlotte LU ; Kristl, Theresa LU ; Bauden, Monika LU ; Rezeli, Melinda LU and Jiang, Yi, et al. (2018) In Oncotarget 9(11). p.9789-9807
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Here we show that shotgun and targeted protein sequencing can be used to identify potential prognostic biomarkers in formalin-fixed paraffin-embedded specimens from 9 patients with PDAC with "short" survival (< 12 months) and 10 patients with "long" survival ( > 45 months) undergoing surgical resection. A total of 24 and 147 proteins were significantly upregulated [fold change ≥2 or ≤0.5 and P < 0.05; or different detection frequencies (≥5 samples)] in patients with "short" survival (including GLUT1) and "long" survival (including C9orf64, FAM96A, CDH1 and CDH17), respectively. STRING analysis of these proteins indicated a tight protein-protein... (More)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Here we show that shotgun and targeted protein sequencing can be used to identify potential prognostic biomarkers in formalin-fixed paraffin-embedded specimens from 9 patients with PDAC with "short" survival (< 12 months) and 10 patients with "long" survival ( > 45 months) undergoing surgical resection. A total of 24 and 147 proteins were significantly upregulated [fold change ≥2 or ≤0.5 and P < 0.05; or different detection frequencies (≥5 samples)] in patients with "short" survival (including GLUT1) and "long" survival (including C9orf64, FAM96A, CDH1 and CDH17), respectively. STRING analysis of these proteins indicated a tight protein-protein interaction network centered on TP53. Ingenuity pathway analysis linked proteins representing "activated stroma factors" and "basal tumor factors" to poor prognosis of PDAC. It also highlighted TCF1 and CTNNB1 as possible upstream regulators. Further parallel reaction monitoring verified that seven proteins were upregulated in patients with "short" survival (MMP9, CLIC3, MMP8, PRTN3, P4HA2, THBS1 and FN1), while 18 proteins were upregulated in patients with "long" survival, including EPCAM, LGALS4, VIL1, CLCA1 and TPPP3. Thus, we verified 25 protein biomarker candidates for PDAC prognosis at the tissue level. Furthermore, an activated stroma status and protein-protein interactions with TP53 might be linked to poor prognosis of PDAC.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarker, Pancreatic ductal adenocarcinoma, Proteome, Survival, Tumor microenvironment
in
Oncotarget
volume
9
issue
11
pages
19 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85040664266
ISSN
1949-2553
DOI
10.18632/oncotarget.23929
language
English
LU publication?
yes
id
060284ce-1ddf-43eb-a8ce-183b927e4122
date added to LUP
2018-03-28 12:35:40
date last changed
2019-03-19 03:51:58
@article{060284ce-1ddf-43eb-a8ce-183b927e4122,
  abstract     = {<p>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Here we show that shotgun and targeted protein sequencing can be used to identify potential prognostic biomarkers in formalin-fixed paraffin-embedded specimens from 9 patients with PDAC with "short" survival (&lt; 12 months) and 10 patients with "long" survival ( &gt; 45 months) undergoing surgical resection. A total of 24 and 147 proteins were significantly upregulated [fold change ≥2 or ≤0.5 and P &lt; 0.05; or different detection frequencies (≥5 samples)] in patients with "short" survival (including GLUT1) and "long" survival (including C9orf64, FAM96A, CDH1 and CDH17), respectively. STRING analysis of these proteins indicated a tight protein-protein interaction network centered on TP53. Ingenuity pathway analysis linked proteins representing "activated stroma factors" and "basal tumor factors" to poor prognosis of PDAC. It also highlighted TCF1 and CTNNB1 as possible upstream regulators. Further parallel reaction monitoring verified that seven proteins were upregulated in patients with "short" survival (MMP9, CLIC3, MMP8, PRTN3, P4HA2, THBS1 and FN1), while 18 proteins were upregulated in patients with "long" survival, including EPCAM, LGALS4, VIL1, CLCA1 and TPPP3. Thus, we verified 25 protein biomarker candidates for PDAC prognosis at the tissue level. Furthermore, an activated stroma status and protein-protein interactions with TP53 might be linked to poor prognosis of PDAC.</p>},
  author       = {Hu, Dingyuan and Ansari, Daniel and Pawlowski, Krzysztof and Zhou, Qimin and Sasor, Agata and Welinder, Charlotte and Kristl, Theresa and Bauden, Monika and Rezeli, Melinda and Jiang, Yi and Marko-Varga, György and Andersson, Roland},
  issn         = {1949-2553},
  keyword      = {Biomarker,Pancreatic ductal adenocarcinoma,Proteome,Survival,Tumor microenvironment},
  language     = {eng},
  number       = {11},
  pages        = {9789--9807},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma},
  url          = {http://dx.doi.org/10.18632/oncotarget.23929},
  volume       = {9},
  year         = {2018},
}