TY - JOUR
T1 - Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma
AU - Hu, Dingyuan
AU - Ansari, Daniel
AU - Pawlowski, Krzysztof
AU - Zhou, Qimin
AU - Sasor, Agata
AU - Welinder, Charlotte
AU - Kristl, Theresa
AU - Bauden, Monika
AU - Rezeli, Melinda
AU - Jiang, Yi
AU - Marko-Varga, György
AU - Andersson, Roland
N1 - Funding Information:
We thank Katarzyna Said Hilmersson, Yutaka Sugihara and Henrik Lindberg for the technical support. The study was supported by SWElife/Vinnova, the Royal Physiographic Society of Lund, the Magnus Bergvall Foundation, the Tore Nilsson Foundation and the Inga and John Hain’s Foundation for Medical Research.
Publisher Copyright:
© Hu et al.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Biomarker
KW - Pancreatic ductal adenocarcinoma
KW - Proteome
KW - Survival
KW - Tumor microenvironment
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U2 - 10.18632/oncotarget.23929
DO - 10.18632/oncotarget.23929
M3 - Article
C2 - 29515771
AN - SCOPUS:85040664266
SN - 1949-2553
VL - 9
SP - 9789
EP - 9807
JO - Oncotarget
JF - Oncotarget
IS - 11
ER -