Co-expression analysis of pancreatic cancer proteome reveals biology and prognostic biomarkers
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ORIGINAL PAPER
Co-expression analysis of pancreatic cancer proteome reveals biology and prognostic biomarkers G. Mantini 1,2 & A. M. Vallés 1 & T. Y. S. Le Large 1,3,4 & M. Capula 2 & N. Funel 5 & T. V. Pham 1 & S. R. Piersma 1 & G. Kazemier 4 & M. F. Bijlsma 5,6 & E. Giovannetti 1,2 & C. R. Jimenez 1 Accepted: 30 June 2020 # The Author(s) 2020
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. A. M. Vallés and T. Y. S. Le Large contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13402-020-00548-y) contains supplementary material, which is available to authorized users. * E. Giovannetti [email protected] * C. R. Jimenez [email protected] 1
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, The Netherlands
2
Fondazione Pisana Per La Scienza, Pisa, Italy
3
Amsterdam UMC, Univ of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, Amsterdam, The Netherlands
4
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands
5
U.O. Anatomia ed Istologia Patologica II Azienda Ospedaliero Universitaria Pisana , Pisa, Italy
6
Oncode Institute, Amsterdam, The Netherlands
Keywords Pancreatic cancer . Protein co-expression . Systems biology . Proteomics . WGCNA . Prognostic biomarkers
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