Oncotarget

Research Papers:

Integrative landscape of dysregulated signaling pathways of clinically distinct pancreatic cancer subtypes

Musalula Sinkala _, Nicola Mulder and Darren Patrick Martin

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:29123-29139. https://doi.org/10.18632/oncotarget.25632

Metrics: PDF 848 views  |   HTML 1921 views  |   ?  


Abstract

Musalula Sinkala1, Nicola Mulder1 and Darren Patrick Martin1

1University of Cape Town, School of Health Sciences, Department of Integrative Biomedical Sciences, Computational Biology Division, Observatory, 7925, South Africa

Correspondence to:

Musalula Sinkala, email: smsinks@icloud.com

Keywords: pancreatic cancer; bioinformatics; signal transduction pathways; integrative analysis; network analysis

Received: April 30, 2018     Accepted: June 04, 2018     Published: June 26, 2018

ABSTRACT

Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients have remained poor. Besides being highly metastatic, pancreatic cancer is challenging to treat because it is caused by a heterogeneous array of somatic mutations that impact a variety of signaling pathways and cellular regulatory systems. Here we use publicly available transcriptomic, copy number alteration and mutation profiling datasets from pancreatic cancer patients together with data on disease outcomes to show that the three major pancreatic cancer subtypes each display distinctive aberrations in cell signaling and metabolic pathways. Importantly, patients afflicted with these different pancreatic cancer subtypes also exhibit distinctive survival profiles. Within these patients, we find that dysregulation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways, and p53 mediated disruptions of cell cycle processes are apparently drivers of disease. Further, we identify for the first time the molecular perturbations of signalling networks that are likely the primary causes of oncogenesis in each of the three pancreatic cancer subtypes.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 25632