Network analysis reveals a signaling regulatory loop in pik3ca-mutated breast predicting survival outcome

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DOIResolve DOI: https://doi.org/10.1016/j.gpb.2017.02.002
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Name affiliation
  1. National Research Council of Canada. Human Health Therapeutics
FormatText, Article
Journal titleGenomics, Proteomics and Bioinformatics
ISSN1672-0229
2210-3244
Volume15
Issue2
Pages121–129
Subjectnetwork analysis; PIK3CA mutation; network motif; breast cancer; genome sequencing; survival
Abstract
Mutated genes are rarely common even in the same pathological type between cancer patients and as such, it has been very challenging to interpret genome sequencing data and difficult to predict clinical outcomes. PIK3CA is one of a few genes whose mutations are relatively popular in tumors. For example, more than 46.6% of luminal-A breast cancer samples have PIK3CA mutated, whereas only 35.5% of all breast cancer samples contain PIK3CA mutations. To understand the function of PIK3CA mutations in luminal A breast cancer, we applied our recently-proposed Cancer Hallmark Network Framework to investigate the network motifs in the PIK3CA-mutated luminal A tumors. We found that more than 70% of the PIK3CA-mutated luminal A tumors contain a positive regulatory loop where a master regulator (PDGF-D), a second regulator (FLT1) and an output node (SHC1) work together. Importantly, we found the luminal A breast cancer patients harboring the PIK3CA mutation and this positive regulatory loop in their tumors have significantly longer survival than those harboring PIK3CA mutation only in their tumors. These findings suggest that the underlying molecular mechanism of PIK3CA mutations in luminal A patients can participate in a positive regulatory loop, and furthermore the positive regulatory loop (PDGF-D/FLT1/SHC1) has a predictive power for the survival of the PIK3CA-mutated luminal A patients.
Publication date
PublisherElsevier
LanguageEnglish
Peer reviewedYes
NPARC number23002172
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