Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma

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Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma. / Hu, Dingyuan; Ansari, Daniel; Pawlowski, Krzysztof; Zhou, Qimin; Sasor, Agata; Welinder, Charlotte; Kristl, Theresa; Bauden, Monika; Rezeli, Melinda; Jiang, Yi; Marko-Varga, György; Andersson, Roland.

In: Oncotarget, Vol. 9, No. 11, 2018, p. 9789-9807.

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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

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

U2 - 10.18632/oncotarget.23929

DO - 10.18632/oncotarget.23929

M3 - Article

VL - 9

SP - 9789

EP - 9807

JO - Oncotarget

T2 - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 11

ER -