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脊髓损伤(SCI)后神经病理性疼痛(NP)相关疾病生物标志物的筛选。

Screening of disease-related biomarkers related to neuropathic pain (NP) after spinal cord injury (SCI).

机构信息

Department of Internal Neurology, The Third Hospital of Jilin University, 126 Xiantai Street, Changchun, 130000, Jilin, People's Republic of China.

Department of Internal Neurology , The Third Hospital of Jilin University , 126 Xiantai Street, Changchun, 130000, Jilin, People's Republic of China.

出版信息

Hum Genomics. 2021 Jan 25;15(1):5. doi: 10.1186/s40246-021-00303-w.

DOI:10.1186/s40246-021-00303-w
PMID:33494823
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7831171/
Abstract

BACKGROUND

Based on the molecular expression level, this paper compares lncRNA and mRNA expressions respectively in peripheral blood samples of the patients after SCI with NP and without NP, and screens disease-related biomarkers related to NP after SCI in peripheral blood samples of patients.

METHOD

The expression spectrum of 25 human peripheral blood samples (12 samples of refractory NP patients after SCI) was downloaded and data were normalized. Screening of GO annotations significantly associated with significant differentially expressed mRNAs and significant involvement of the KEGG pathway. The WGCNA algorithm was used to screen for modules and RNAs that were significantly associated with disease characterization. A co-expression network was constructed to extract the genes involved in the disease pathway from the co-expression network, construct a network of SCI pain-related pathways, and screen important disease-related biomarkers. Quantitative real-time PCR was used to detect the mRNA expression of hub genes.

RESULTS

Data were normalized and re-annotated by detection of platform information, resulting in a total of 289 lncRNA and 18197 mRNAs. Screening resulted in 338 significant differentially expressed RNAs that met the threshold requirements. Differentially expressed RNAs were significantly enriched with the brown and magenta modules. Six KEGG signaling pathways were screened in the co-expression network, and three KEGG pathways with direct neuropathic pain were identified. The expression levels of E2F1, MAX, MITF, CTNNA1, and ADORA2B in the disease group were all significantly upregulated (p < 0.01). Compared with the normal group, the expression of OXTR was upregulated.

CONCLUSION

We speculate that there are 7 genes and 2 lncRNAs directly involved in the pain pathway: E2F1, MAX, MITF, CTNNA1, ADORA2B, GRIK3, OXTR, LINC01119, and LINC02447. These molecules may be important for NP after SCI.

摘要

背景

基于分子表达水平,本文分别比较了 NP 患者和非 NP 患者 SCI 后外周血样本中的 lncRNA 和 mRNA 表达,并筛选了 SCI 患者外周血样本中与 NP 相关的疾病相关生物标志物。

方法

下载 25 个人类外周血样本(12 例 SCI 后难治性 NP 患者)的表达谱,对数据进行归一化。筛选与显著差异表达的 mRNAs 显著相关的 GO 注释和显著参与的 KEGG 通路。使用 WGCNA 算法筛选与疾病特征显著相关的模块和 RNA。构建共表达网络,从共表达网络中提取疾病途径相关基因,构建 SCI 疼痛相关途径网络,筛选重要疾病相关生物标志物。采用实时定量 PCR 检测核心基因的 mRNA 表达。

结果

通过检测平台信息对数据进行归一化和重新注释,共得到 289 个 lncRNA 和 18197 个 mRNA。筛选出 338 个满足阈值要求的显著差异表达 RNA。差异表达 RNA 与棕色和紫红色模块显著富集。在共表达网络中筛选出 6 条 KEGG 信号通路,确定了 3 条与直接神经病理性疼痛相关的 KEGG 通路。疾病组中 E2F1、MAX、MITF、CTNNA1 和 ADORA2B 的表达水平均显著上调(p<0.01)。与正常组相比,OXTR 的表达上调。

结论

我们推测有 7 个基因和 2 个 lncRNA 直接参与疼痛途径:E2F1、MAX、MITF、CTNNA1、ADORA2B、GRIK3、OXTR、LINC01119 和 LINC02447。这些分子可能对 SCI 后 NP 很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/cad39829de92/40246_2021_303_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/64395ec3a061/40246_2021_303_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/e2c3c5df2709/40246_2021_303_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/1e88f732f22c/40246_2021_303_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/90f717f0438f/40246_2021_303_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/cad39829de92/40246_2021_303_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/64395ec3a061/40246_2021_303_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/c565f0edf135/40246_2021_303_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/521cc04cc6eb/40246_2021_303_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/1fcc0cc403a2/40246_2021_303_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/e2c3c5df2709/40246_2021_303_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/1e88f732f22c/40246_2021_303_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/90f717f0438f/40246_2021_303_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7831171/cad39829de92/40246_2021_303_Fig8_HTML.jpg

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