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Exploring MicroRNA Patterns as Biomarkers of FOLFOX Chemotherapy-Induced Peripheral Neuropathy in Patients with Colorectal Cancer

ABSTRACT: This study aimed to identify potential miRNA-based biomarkers that can predict FOLFOX-CIPN symptoms. High throughput microRNA sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤three cycles and those who underwent ≥six cycles of FOLFOX chemotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE260661 | GEO | 2024/03/06

REPOSITORIES: GEO

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Prognosis of Stage III Colorectal Carcinomas with FOLFOX Adjuvant Chemotherapy can be Predicted by Molecular Subtype

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FBXW4 acts as a protector of FOLFOX-based Chemotherapy in Metastatic Colorectal Cancer Identified by Co-expression network analysis

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Plasma Proteomic Characterization of Colorectal Cancer Patients with FOLFOX Chemotherapy

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Global proteome changes in liver tissue 6 weeks after FOLFOX treatment of colorectal cancer liver metastases.

Project description:Study: Oxaliplatin-based chemotherapy for colorectal liver metastasis is associated with sinusoidal injury of liver parenchyma and may result in increased morbidity after liver surgery. Preclinical and human liver parenchyma studies have proposed several pathways of oxaliplatin-induced injury, but the effects on protein level remains unknown. Protein expression in liver tissue from eight patients treated with FOLFOX and seven controls without treatment was analyzed by label-free liquid chromatography mass spectrometry. Conclusion: Six weeks after FOLFOX treatment less than 1% of identified proteins showed changes in expression. The changes were associated with DNA replication, cell cycle entry and innate immune response. We hypothesize that the changes are residual after recovery from FOLFOX treatment injury.

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Project description: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.

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Identifying Predictors Of Taxane-Induced Peripheral Neuropathy Using Mass Spectrometry-based Proteomics Technology

Project description:In this study, we evaluated the association between protein content in serum exosomes and severity of CIPN. Women with early stage breast cancer receiving adjuvant taxane chemotherapy were assessed with the FACT-Ntx score and serum was collected before and after the taxane treatment.

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