Dataset Information

Gene expression signatures of chemotherapy-induced neuropathy induced by cisplatin and oxaliplatin

ABSTRACT: Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents for the treatment of several cancer types. However, a main side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which may lead to decreased quality of life, changes in chemotherapeutic treatment or even treatment cessation. Although painful symptoms associated with CIPN are faithfully recapitulated by mouse models, there is limited knowledge of how these drugs affect the expression of genes in peripheral sensory neurons. The present study carried out a transcriptomic analysis of dorsal root ganglia isolated from mice treated with vincristine, oxaliplatin, and cisplatin with a view to gain insight into the comparative pathophysiological mechanisms of CIPN. RNA-Seq using 75-nucleotide single end runs revealed 368, 295 and 256 differential expressed genes (DEGs) induced by treatment with vincristine, oxaliplatin and cisplatin, respectively. Although there were many similarities in DEGs between chemotherapeutic agents, only 5 genes were dysregulated in all groups. Cell type enrichment analysis (CTEA) and gene set enrichment analysis (GSEA) 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 inflammatory and neuropathic gene expression signature. Only ‘regulation of transport’ and ‘response to external stimuli’ were gene ontology terms shared between all treatments. These results provide insight into the recruitment of innate and adaptive immune responses to DRG tissue and indicate enhanced neuro-inflammatory processes following administration of vincristine, oxaliplatin, and cisplatin. These gene expression signatures may provide insight into novel drug targets for treatment of CIPN.

ORGANISM(S): Mus musculus

PROVIDER: GSE125002 | GEO | 2019/06/01

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Time-course and concentration-effect experiments with multiple time points and drug concentrations provide far more valuable information than experiments with just two design-points (treated vs. control), as commonly performed in most microarray studies. Analysis of the data from such complex experiments, however, remains a challenge. Here we present a semi-automated method for fitting time profiles and concentration-effect patterns, simultaneously, to gene expression data. The submodels for time-course included exponential increase and decrease models with parameters such as initial expression level, maximum effect, and rate-constant (or half-time). The submodel for concentration-effect was a 4-parameter Hill model. The method was applied to an Affymetrix HG-U95Av2 dataset consisting of 51 arrays. The specific study focused on the effects of two platinum drugs, cisplatin and oxaliplatin, on A2780 human ovarian carcinoma cells. Replicates were available at most time points and concentrations. Eighteen genes were selected; time-course and concentration-effect were modeled simultaneously. Comparisons of model parameters helped distinguish genes with different expression patterns between the two drug treatments. This overall paradigm can help in understanding the molecular mechanisms of the agents, and the timing of their actions. Experiment Overall Design: For the time-course experiments, samples were exposed to IC90 concentrations of oxaliplatin (32 Î¼M) or cisplatin (25 Î¼M) for 2 hours, and then allowed to grow in drug free medium. Cells were harvested and processed at the following times: before treatment, immediately after treatment (0 h), and at 2 h, 6 h, 16 h and 24 h after treatment. Control experiments were done following a similar design, but with exposure to drug-free medium. For the concentration-effect experiments, samples were treated with specific growth-inhibitory concentrations of cisplatin or oxaliplatin for 2 hours. The previously-estimated IC10, IC25, IC50, IC75 and IC90 concentrations (for 2 hr drug exposure; 72 hr total growth) for cisplatin and oxaliplatin growth inhibition of A2780 were 2.6, 4.0, 6.4, 12 and 25 Î¼M and 2.8, 4.8, 8.5, 17 and 32 Î¼M respectively. Cells were harvested and processed at 16 h after completion of treatment

Dataset Information

Gene expression signatures of chemotherapy-induced neuropathy induced by cisplatin and oxaliplatin

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure