Abstract
Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents
for the treatment of many tumors. However, a main side effect is chemotherapy-induced
peripheral neuropathy (CIPN), which may lead to changes in chemotherapeutic treatment.
Although symptoms associated with CIPN are recapitulated by mouse models, there is
limited knowledge of how these drugs affect the expression of genes in sensory neurons.
The present study carried out a transcriptomic analysis of dorsal root ganglia following
vincristine, oxaliplatin, and cisplatin treatment with a view to gain insight into
the comparative pathophysiological mechanisms of CIPN. RNA-Seq revealed 368, 295,
and 256 differential expressed genes induced by treatment with vincristine, oxaliplatin,
and cisplatin, respectively, and only 5 shared genes were dysregulated in all 3 groups.
Cell type enrichment analysis and gene set enrichment analysis showed predominant
effects on genes associated with the immune system after treatment with vincristine,
while oxaliplatin treatment affected mainly neuronal genes. Treatment with cisplatin
resulted in a mixed gene expression signature.
Perspective
These results provide insight into the recruitment of immune responses to dorsal root
ganglia and indicate enhanced neuroinflammatory processes following administration
of vincristine, oxaliplatin, and cisplatin. These gene expression signatures may provide
insight into novel drug targets for treatment of CIPN.
Key words
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Article info
Publication history
Published online: June 28, 2019
Accepted:
June 13,
2019
Received in revised form:
June 4,
2019
Received:
March 19,
2019
Footnotes
IV and JD were supported by NHMRC Research fellowships. HS and AM were supported by Australian Government research scholarships.
Disclosures: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
There are no conflicts of interest.
Identification
Copyright
© 2019 by United States Association for the Study of Pain, Inc.
