Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma

Dingyuan Hu, Daniel Ansari, Krzysztof Pawlowski, Qimin Zhou, Agata Sasor, Charlotte Welinder, Theresa Kristl, Monika Bauden, Melinda Rezeli, Yi Jiang, György Marko-Varga, Roland Andersson

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)9789-9807
Number of pages19
JournalOncotarget
Volume9
Issue number11
DOIs
StatePublished - 2018

Keywords

  • Biomarker
  • Pancreatic ductal adenocarcinoma
  • Proteome
  • Survival
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology

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