Volume 25, Issue 4 pp. 366-376
RESEARCH REPORT

Co-expression gene modules involved in cisplatin-induced peripheral neuropathy according to sensitivity, status, and severity

Rui-Hao Zhou

Rui-Hao Zhou

Department of Pain Management, West China Hospital, Sichuan University, Chengdu, China

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Chan Chen

Chan Chen

Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China

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Su-Han Jin

Su-Han Jin

Department of Orthodontics, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China

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Jun Li

Jun Li

Department of Pain Management, West China Hospital, Sichuan University, Chengdu, China

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Zi-Hao Xu

Zi-Hao Xu

School of Public Health, Nanchang University, Nanchang, China

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Ling Ye

Corresponding Author

Ling Ye

Department of Pain Management, West China Hospital, Sichuan University, Chengdu, China

Correspondence

Ling Ye, Department of Pain Management, West China Hospital, Sichuan University, Guoxuexiang No. 37, Chengdu 610000, China.

Email: [email protected]

Jian-Guo Zhou, Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Email: [email protected]

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Jian-Guo Zhou

Corresponding Author

Jian-Guo Zhou

Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, China

Department of Radiation Oncology, Universitätsklinikum Erlangen, Erlangen, Germany

Correspondence

Ling Ye, Department of Pain Management, West China Hospital, Sichuan University, Guoxuexiang No. 37, Chengdu 610000, China.

Email: [email protected]

Jian-Guo Zhou, Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Email: [email protected]

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First published: 11 August 2020
Citations: 3

Rui-Hao Zhou and Chan Chen contributed equally to this study and should be considered as co-first authors.

Funding information: 1·3·5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University, Grant/Award Number: 2019HXFH069; Science and Technology Department of Sichuan Province, Grant/Award Number: 2020YJ0283

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is among the most disabling and frustrating problems for cancer survivors. The neurotoxicity caused by cisplatin varies greatly among patients, and few predictors of appearance, duration of symptoms, susceptibility, or severity are available. A deeper understanding of the mechanisms underlying individual differences in status, severity, or sensitivity in response to cisplatin treatment is therefore required. By analyzing the GSE64174 gene expression profile and constructing a weighted gene co-expression network analysis (WGCNA) network, we screened gene modules and hub genes related to CIPN status, severity and sensitivity. We first identified the transcriptome profile of mouse dorsal root ganglion (DRG) samples and transformed their genes to human DRG counterparts. We then constructed WGCNA gene modules via optimal soft-threshold power-identification and module-preservation analysis. Comprehensive analysis and identification of module hub genes were performed via functional-enrichment analysis and significant common hub genes were identified, including “Cytoscape_cytoHubba,” “Cytoscape_MCODE,” and “Metascape_MCODE.” Brown, green, and blue modules were selected to represent CIPN sensitivity, status, and severity, respectively, via trait-module correlational analysis. Additionally, functional enrichment analysis results indicated that these three modules were associated with some crucial biological functions, such as neutrophil migration, chemokine-mediated signaling pathway, and PI3K-Akt signaling pathway. We then identified seven common hub genes via three methods, including CXCL10, CCL21, CCR2, CXCR4, TLR4, NPY1R, and GALR2, related to CIPN status, severity and sensitivity. Our results provide possible targets and mechanism insights into the development and progress of CIPN, which can guide further transformation and pre-clinical research.

CONFLICT OF INTEREST

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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