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.
Original language | English |
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Pages (from-to) | 1147-1159 |
Number of pages | 13 |
Journal | Cellular oncology |
Volume | 43 |
Issue number | 6 |
Early online date | 2020 |
DOIs | |
Publication status | Published - Dec 2020 |
Keywords
- Pancreatic cancer
- Prognostic biomarkers
- Protein co-expression
- Proteomics
- Systems biology
- WGCNA