Identification of Biomarkers Related to Neuropathic Pain Induced by Peripheral Nerve Injury

Zhang, Chunguo; Wan, Hongquan; Ma, Kening; Luan, Shuxin; He, Li

doi:10.1007/s12031-019-01322-y

Cited by 10 publications

(9 citation statements)

References 34 publications

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Section: Discussionmentioning

confidence: 99%

“…While no studies have examined associations between PIPN and changes in gene expression or methylation of MAP2K2, expression of Map2k2 increased in rat L4 and L5 DRGs cells with sciatic nerve lesions as compared with sham controls three days after injury. 107 The transferrin receptor (TFRC) gene encodes for a protein important for cellular iron uptake and homeostatis. 108 TFRC (TFR1) is a key iron metabolism gene that fine tunes cellular iron access, storage, and utilization.…”

Section: Hif-1 Signaling Pathway Genes Associated With Dm and Dgementioning

confidence: 99%

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Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain

et al. 2020

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Background Paclitaxel is an important chemotherapeutic agent for the treatment of breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a major dose-limiting toxicity that can persist into survivorship. While not all survivors develop PIPN, for those who do, it has a substantial negative impact on their functional status and quality of life. No interventions are available to treat PIPN. In our previous studies, we identified that the HIF-1 signaling pathway (H1SP) was perturbed between breast cancer survivors with and without PIPN. Preclinical studies suggest that the H1SP is involved in the development of bortezomib-induced and diabetic peripheral neuropathy, and sciatic nerve injury. The purpose of this study was to identify H1SP genes that have both differential methylation and differential gene expression between breast cancer survivors with and without PIPN. Methods A multi-staged integrated analysis was performed. In peripheral blood, methylation was assayed using microarray and gene expression was assayed using RNA-seq. Candidate genes in the H1SP having both differentially methylation and differential expression were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN. Then, candidate genes were evaluated for differential methylation and differential expression in public data sets of preclinical models of PIPN and sciatic nerve injury. Results Eight candidate genes were identified as both differential methylation and differential expression in survivors. Of the eight homologs identified, one was found to be differential expression in both PIPN and “normal” mice dorsal root ganglia; three were differential methylation in sciatic nerve injury versus sham rats in both pre-frontal cortex and T-cells; and two were differential methylation in sciatic nerve injury versus sham rats in the pre-frontal cortex. Conclusions This study is the first to evaluate for methylation in cancer survivors with chronic PIPN. The findings provide evidence that the expression of H1SP genes associated with chronic PIPN in cancer survivors may be regulated by epigenetic mechanisms and suggests genes for validation as potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Hif-1 Signaling Pathway Genes Associated With Dm and Dgementioning

confidence: 99%

Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain

et al. 2020

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“…11 Neuropathic pain, characterized by the presence of allodynia, spontaneous pain, sensory loss, and/or hyperalgesia, may occur after nerve injury. 15 As observed in patients with chronic OA pain and CRPS, neuropathic pain involves both peripheral and central sensitization. 16 One study reported significantly elevated serum levels of 4 different haptoglobin isoforms and significantly decreased serum levels of transthyretin and a-2 macroglobulin in nerve compression model mice compared with healthy controls (Table ), with normalization of levels in compression model mice treated with gabapentin.…”

Section: Molecular Biomarkersmentioning

confidence: 99%

Diagnostic Biomarkers for Upper Extremity Chronic Pain Conditions

Gary¹,

Horowitz²,

Giladi³

2023

Journal of Hand Surgery Global Online

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“…The upregulation of parkin levels could, in turn, contribute to the activation of p53 at the transcriptional level, which could explain, at least in part, the increased cellular apoptotic commitment in cerebral cancer 11 . Previous studies have demonstrated that the inhibition of p53 could be an important indicator for the treatment of neuropathic symptoms 12,13 .…”

Section: Introductionmentioning

confidence: 99%

p53 Knock Out Mice Enhances Anxiety- and Depression-Like Behaviors through an Increase of Glutamate, Calcium, and Cytokine-Mediated Cell Death Signals

Yeo

Yoo

et al. 2021

Preprint

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Extensive epidemiological evidence indicates that patients with certain cancers have a lower probability of developing some types of neurodegenerative diseases (ND) and mood disorders and vice versa. These inverse comorbidities may be associated with several different molecular processes. p53, is a potentially responsible for regulating the development of ND, mood disorders as well as cancers. To investigate whether the tumor suppressor p53 may be associated with ND development, we studied the behavioral changes in p53 knockout (p53−/−) mice and possible action mechanisms. Increased anxiety-like but not depression-like behaviors were displayed in p53−/− mice without impaired motor activities under the non-chronic unpredictable mild stress condition. However, in the p53−/− mice, more anxiety-like and depression-like behaviors were observed in the chronic unpredictable mild stress (CUMS) condition. Our mechanism studies showed that brain-derived neurotrophic factor (BDNF) protein was significantly downregulated, but glutamate levels were significantly increased in the prefrontal cortex of p53−/− mice. Further analyses showed that the p53−/− mice caused more stress-induced nerve damage as a result of an increase in intracellular calcium levels and N-methyl D-aspartate receptor subtype 2B (NMDAR2B) expression. Treatment with corticosterone (mimics CUMS in vitro) increased glutamate levels, NMDAR2B expression, and calcium levels, and these levels were elevated by co-treatment with pifithrin-α (p53 inhibitor) in PC12 cells. Cell death and cell death-mediated signals (p-p38, p-JNK and caspase-3) were upregulated, but neuroprotective signals (BDNF p-Akt, p-ERK and p-CREB) were downregulated in p53−/− mice, and corticoid and/or pifithrin-α treated PC12 cells. These data indicate that p53 may be an important preventive factor against depression and anxiety, and thus suggests a possible correlation between cancer and anxiety/depression development. Running title: Deficiency of p53 enhances mental disorder

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Identification of Biomarkers Related to Neuropathic Pain Induced by Peripheral Nerve Injury

Cited by 10 publications

References 34 publications

Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain

Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain

Diagnostic Biomarkers for Upper Extremity Chronic Pain Conditions

p53 Knock Out Mice Enhances Anxiety- and Depression-Like Behaviors through an Increase of Glutamate, Calcium, and Cytokine-Mediated Cell Death Signals

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