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. 2019 Oct 15:335:577019.
doi: 10.1016/j.jneuroim.2019.577019. Epub 2019 Aug 2.

Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors

Christine Miaskowski  1 , Kimberly Topp  2 , Yvette P Conley  3 , Steven M Paul  1 , Michelle Melisko  2 , Mark Schumacher  2 , Margaret Chesney  2 , Gary Abrams  2 , Jon D Levine  2 , Kord M Kober  4
Affiliations

Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors

Christine Miaskowski et al. J Neuroimmunol. .

Abstract

Paclitaxel is a common chemotherapy drug associated with the development of chronic paclitaxel-induced peripheral neuropathy (PIPN). PIPN is associated with neuroinflammatory mechanisms in pre-clinical studies. Here, we evaluated for differential gene expression (DGE) in peripheral blood between breast cancer survivors with and without PIPN and for neuroinflammatory (NI) related signaling pathways and whole-transcriptome profiles from other experiments. Pathway impact analysis identified 8 perturbed NI related pathways. Expression profile analysis found 15 experiments having similar whole-transcriptome profiles of DGE related to neuroinflammation and PIPN. These findings suggest that perturbations in pathways associated with neuroinflammation are found in cancer survivors with PIPN.

Keywords: Breast cancer; Chemokines; Cytokines; Differential gene expression; Neuroinflammation; Neuropathy; Paclitaxel; Pathway analysis; Survivor; Taxanes.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

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Graphical abstract
Fig. 1
Fig. 1
An overview of the analytic approach used to evaluate for neuroinflammation related pathways and gene expression experiments associated with paclitaxel-induced peripheral neuropathy (PIPN). Differential gene expression (DGE) in peripheral blood was found between breast cancer survivors with (P) and without (N) paclitaxel-induced peripheral neuropathy and evaluated for (1) perturbed neuroinflammation related signaling pathways using pathway impact analysis and (2) experiments from the gene expression omnibus (GEO) with similar whole-transcriptome profiles of differential gene expression related to neuroinflammation and PIPN using expression profile analysis. Taken together, our results suggest that perturbations in pro- and anti-inflammatory pathways associated with neuroinflammation are found in cancer survivors with PIPN.
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