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ABSTRACT: Purpose
Despite extensive biological and clinical studies, including comprehensive genomic and transcriptomic profiling efforts, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease, with a poor survival and limited therapeutic options. The goal of this study was to assess co-expressed PDAC proteins and their associations with biological pathways and clinical parameters.Methods
Correlation network analysis is emerging as a powerful approach to infer tumor biology from omics data and to prioritize candidate genes as biomarkers or drug targets. In this study, we applied a weighted gene co-expression network analysis (WGCNA) to the proteome of 20 surgically resected PDAC specimens (PXD015744) and confirmed its clinical value in 82 independent primary cases.Results
Using WGCNA, we obtained twelve co-expressed clusters with a distinct biology. Notably, we found that one module enriched for metabolic processes and epithelial-mesenchymal-transition (EMT) was significantly associated with overall survival (p?=?0.01) and disease-free survival (p?=?0.03). The prognostic value of three proteins (SPTBN1, KHSRP and PYGL) belonging to this module was confirmed using immunohistochemistry in a cohort of 82 independent resected patients. Risk score evaluation of the prognostic signature confirmed its association with overall survival in multivariate analyses. Finally, immunofluorescence analysis confirmed co-expression of SPTBN1 and KHSRP in Hs766t PDAC cells.Conclusions
Our WGCNA analysis revealed a PDAC module enriched for metabolic and EMT-associated processes. In addition, we found that three of the proteins involved were associated with PDAC survival.
SUBMITTER: Mantini G
PROVIDER: S-EPMC7716908 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Cellular oncology (Dordrecht, Netherlands) 20200829 6
<h4>Purpose</h4>Despite extensive biological and clinical studies, including comprehensive genomic and transcriptomic profiling efforts, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease, with a poor survival and limited therapeutic options. The goal of this study was to assess co-expressed PDAC proteins and their associations with biological pathways and clinical parameters.<h4>Methods</h4>Correlation network analysis is emerging as a powerful approach to infer tumor biology ...[more]