Disease-related protein co-expression networks are associated with the prognosis of resectable node-positive pancreatic ductal adenocarcinoma.
Adenocarcinoma
/ metabolism
Carcinoma, Pancreatic Ductal
/ genetics
Endoribonucleases
/ metabolism
Gene Expression Regulation, Neoplastic
Hedgehog Proteins
/ metabolism
Humans
Pancreatic Ducts
/ pathology
Pancreatic Neoplasms
/ genetics
Prognosis
Protein Serine-Threonine Kinases
Pancreatic Neoplasms
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 08 2022
29 08 2022
Historique:
received:
09
04
2022
accepted:
25
08
2022
entrez:
29
8
2022
pubmed:
30
8
2022
medline:
1
9
2022
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is a multifactorial disease, the molecular profile of which remains unclear. This study aimed at unveiling the disease-related protein networks associated with different outcomes of resectable, node-positive PDAC cases. We assessed laser-microdissected cancerous cells from PDAC tissues of a poor outcome group (POG; n = 4) and a better outcome group (BOG; n = 4). Noncancerous pancreatic duct tissues (n = 5) were used as the reference. We identified four representative network modules by applying a weighted network correlation analysis to the obtained quantitative PDAC proteome datasets. Two network modules that were significant for POG were associated with the heat shock response to hypoxia-related stress; in the latter, a large involvement of the non-canonical Hedgehog pathway (regulated by GLI1), the internal ribosome entry site-mediated cap-independent translation, the inositol requiring enzyme 1-alpha (IRE1α)/X-box binding protein 1 pathway of the unfolding protein response (UPR), and the aerobic glycolysis was observed. By contrast, the BOG characteristic module was involved in the inactivation of the UPR pathway via the synoviolin 1-dependent proteasomal degradation of IRE1α, the activation of SOX2, and the loss of PALB2 (partner and localizer of BRCA2) function, all potentially suppressing malignant tumor development. Our findings might facilitate future therapeutic strategies for PDAC.
Identifiants
pubmed: 36038612
doi: 10.1038/s41598-022-19182-9
pii: 10.1038/s41598-022-19182-9
pmc: PMC9424258
doi:
Substances chimiques
Hedgehog Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Endoribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14709Informations de copyright
© 2022. The Author(s).
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