Dataset Information

Differential transcriptome profile of peripheral white cells to identify biomarkers involved in oxaliplatin induced neuropathy.

ABSTRACT: Anticancer chemotherapy (CT) produces non-desirable effects on normal healthy cells and tissues. Oxaliplatin is widely used in the treatment of colorectal cancer and responsible for the development of sensory neuropathy in varying degrees, from complete tolerance to chronic neuropathic symptoms. We studied the differential gene expression of peripheral leukocytes in patients receiving oxaliplatin-based chemotherapy to find genes and pathways involved in oxaliplatin-induced peripheral neuropathy. Circulating white cells were obtained prior and after three cycles of FOLFOX or CAPOX chemotherapy from two groups of patients: with or without neuropathy. RNA was purified, and transcriptomes were analyzed. Differential transcriptomics revealed a total of 502 genes, which were significantly up- or down-regulated as a result of chemotherapy treatment. Nine of those genes were expressed in only one of two situations: CSHL1, GH1, KCMF1, IL36G and EFCAB8 turned off after CT, and CSRP2, IQGAP1, GNRH2, SMIM1 and C5orf17 turned on after CT. These genes are likely to be associated with the onset of oxaliplatin-induced peripheral neuropathy. The quantification of their expression in peripheral white cells may help to predict non-desirable side effects and, consequently, allow a better, more personalized chemotherapy.

SUBMITTER: Morales M

PROVIDER: S-EPMC4263976 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential transcriptome profile of peripheral white cells to identify biomarkers involved in oxaliplatin induced neuropathy.

Morales Manuel M Ávila Julio J González-Fernández Rebeca R Boronat Laia L Soriano María Luisa ML Martín-Vasallo Pablo P

Journal of personalized medicine 20140605 2

Anticancer chemotherapy (CT) produces non-desirable effects on normal healthy cells and tissues. Oxaliplatin is widely used in the treatment of colorectal cancer and responsible for the development of sensory neuropathy in varying degrees, from complete tolerance to chronic neuropathic symptoms. We studied the differential gene expression of peripheral leukocytes in patients receiving oxaliplatin-based chemotherapy to find genes and pathways involved in oxaliplatin-induced peripheral neuropathy. ...[more]

PMID: 25563226

Similar Datasets

Project description:BackgroundOxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora.MethodsIn this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora's role in HGWD for chronic OIPN by pain scoring and related pathological analysis.ResultsHGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis.ConclusionsHGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.

Project description:BackgroundOxaliplatin-induced peripheral neuropathy (OIPN) has significant clinical impact on the quality of life for cancer patients and is a dose limiting toxicity. Trials studying preventive measures have been inconclusive. A systematic review and meta-analysis were conducted to evaluate the existing pharmacological and non-pharmacological interventions to prevent chronic OIPN.MethodsLiterature databases PubMed-MEDLINE, Embase and Scopus, were searched from 1 Jan 2005 to 08 Aug 2020 and major conferences' abstracts were reviewed for randomized controlled trials that examined the efficacy of any preventive measure for OIPN. The primary outcome measure was the incidence of chronic OIPN with a preventive intervention as compared to placebo or no intervention. The pooled risk ratio and its 95% confidence interval were calculated using a random effects model. A network meta-analysis was conducted to derive indirect evidence of any preventive effect of an intervention against placebo when original trials compared one intervention against another.ResultsForty-four trials were analyzed describing 29 chemoprotective interventions, including combinations, and 1 non-pharmacological intervention. Ratings were assessed via a combination of outcomes with quality assessment using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Of the 30 interventions examined, there were six interventions supporting potential efficacy, 11 interventions with insufficient evidence and 13 interventions not recommended.ConclusionCurrently, there is insufficient certainty to support any intervention as effective in preventing OIPN. Of note is that most of these studies have focused on pharmacological interventions; non-pharmacological interventions are underexplored. Further research on ways to limit OIPN is needed.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=225095, Prospero Registration Number: CRD42021225095.

Project description:Chemotherapy-induced peripheral neuropathy is a frequent, disabling side effect of anticancer drugs. Oxaliplatin, a platinum compound used in the treatment of advanced colorectal cancer, often leads to a form of chemotherapy-induced peripheral neuropathy characterized by mechanical and cold hypersensitivity. Current therapies for chemotherapy-induced peripheral neuropathy are ineffective, often leading to the cessation of treatment. Transient receptor potential ankyrin 1 (TRPA1) is a polymodal, non-selective cation-permeable channel expressed in nociceptors, activated by physical stimuli and cellular stress products. TRPA1 has been linked to the establishment of chemotherapy-induced peripheral neuropathy and other painful neuropathic conditions. Sigma-1 receptor is an endoplasmic reticulum chaperone known to modulate the function of many ion channels and receptors. Sigma-1 receptor antagonist, a highly selective antagonist of Sigma-1 receptor, has shown effectiveness in a phase II clinical trial for oxaliplatin chemotherapy-induced peripheral neuropathy. However, the mechanisms involved in the beneficial effects of Sigma-1 receptor antagonist are little understood. We combined biochemical and biophysical (i.e. intermolecular Förster resonance energy transfer) techniques to demonstrate the interaction between Sigma-1 receptor and human TRPA1. Pharmacological antagonism of Sigma-1R impaired the formation of this molecular complex and the trafficking of functional TRPA1 to the plasma membrane. Using patch-clamp electrophysiological recordings we found that antagonists of Sigma-1 receptor, including Sigma-1 receptor antagonist, exert a marked inhibition on plasma membrane expression and function of human TRPA1 channels. In TRPA1-expressing mouse sensory neurons, Sigma-1 receptor antagonists reduced inward currents and the firing of actions potentials in response to TRPA1 agonists. Finally, in a mouse experimental model of oxaliplatin neuropathy, systemic treatment with a Sigma-1 receptor antagonists prevented the development of painful symptoms by a mechanism involving TRPA1. In summary, the modulation of TRPA1 channels by Sigma-1 receptor antagonists suggests a new strategy for the prevention and treatment of chemotherapy-induced peripheral neuropathy and could inform the development of novel therapeutics for neuropathic pain.

Dataset Information

Differential transcriptome profile of peripheral white cells to identify biomarkers involved in oxaliplatin induced neuropathy.

Publications

Differential transcriptome profile of peripheral white cells to identify biomarkers involved in oxaliplatin induced neuropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets