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鉴定Cbx6作为肾缺血/再灌注损伤的潜在生物标志物。

Identification of Cbx6 as a potential biomarker in renal ischemia/reperfusion injury.

作者信息

Pan Ziwen, Chang Sheng, Chen Song, Zou Zhiyu, Hou Yibo, Chen Zhishui, Zhang Weijie

机构信息

Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China.

Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China.

出版信息

Transpl Immunol. 2024 Jun;84:102018. doi: 10.1016/j.trim.2024.102018. Epub 2024 Mar 5.

Abstract

BACKGROUND

Renal ischemia/reperfusion injury (RIRI) is an inevitable consequence of kidney transplantation and has a negative impact on both short-term and long-term graft survival. The identification of key markers in RIRI to improve the prognosis of patients would be highly advantageous.

METHODS

Gene expression profile data of GSE27274 were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed using the Limma package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of DEGs were performed. Support vector machine-recursive feature elimination and least absolute shrinkage and selection operator regression modeling were both performed to identify potential biomarkers. The GSE148420 dataset, quantitative reverse transcriptase-PCR, and western blotting results of kidney tissue samples were used to validate the bioinformatic analysis. Lastly, exploring differences between different groups through gene set enrichment analysis and using DsigDB database to identify potential therapeutic drugs targeting hub genes.

RESULTS

A total of 160 upregulated and 180 downregulated DEGs were identified. Functional enrichment analysis identified significant enrichment in processes involving peroxisomes. As a subunit of Polycomb Repressive Complex 1(PRC1), chromobox 6(Cbx6) was identified as a potential biomarker with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval 0.624-1.000) in the validation cohort, and it was highly expressed in the RIRI group (p < 0.05). In the high expression group Cbx6 was more enriched in the toll-like receptor signaling pathway. We predicted 15 potential drugs targeting hub genes of RIRI.

CONCLUSIONS

We identified Cbx6 as a potential biomarker for RIRI and 15 potential drugs for the treatment of RIRI, which might shed a light on the treatment of RIRI.

摘要

背景

肾缺血/再灌注损伤(RIRI)是肾移植不可避免的后果,对移植肾的短期和长期存活均有负面影响。识别RIRI中的关键标志物以改善患者预后将非常有益。

方法

从基因表达综合数据库获取GSE27274的基因表达谱数据。使用Limma软件包分析差异表达基因(DEG)。对DEG进行基因本体论和京都基因与基因组百科全书富集分析。进行支持向量机递归特征消除和最小绝对收缩和选择算子回归建模以识别潜在生物标志物。使用GSE148420数据集、定量逆转录PCR和肾组织样本的蛋白质印迹结果验证生物信息学分析。最后,通过基因集富集分析探索不同组之间的差异,并使用DsigDB数据库识别靶向枢纽基因的潜在治疗药物。

结果

共鉴定出160个上调和180个下调的DEG。功能富集分析确定在涉及过氧化物酶体的过程中有显著富集。作为多梳抑制复合物1(PRC1)的一个亚基,染色体盒蛋白6(Cbx6)被鉴定为潜在生物标志物,在验证队列中的受试者工作特征曲线下面积为0.875(95%置信区间0.624 - 1.000),且在RIRI组中高表达(p < 0.05)。在高表达组中,Cbx6在Toll样受体信号通路中更富集。我们预测了15种靶向RIRI枢纽基因的潜在药物。

结论

我们鉴定出Cbx6作为RIRI的潜在生物标志物和15种治疗RIRI的潜在药物,这可能为RIRI的治疗提供线索。

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