He Yi-Ran, Ding Ni, Han Ming-Chen, He Hong-Yu, Xuan Li-Zhen, Gu Zhun-Yong, Zhong Ming, Ju Min-Jie
Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
Discov Oncol. 2024 Dec 5;15(1):749. doi: 10.1007/s12672-024-01651-4.
Sepsis and cancer are both leading causes of death worldwide, and they share several pathophysiological characteristics. Some studies have suggested a possible association between sepsis and cancer; however, few have investigated the core genes involved in both diseases.
Core genes common to both sepsis and cancer were identified using pediatric sepsis datasets (GEO: GSE26378, GSE4607, GSE8121 and GSE13904) and cancer databases (TCGA: BRCA, COADREAD, ESCA, KIRC, LIHC, LUAD, STAD). Gene Ontology (GO) and Reactome enrichment analyses, along with a protein-protein interaction (PPI) network analysis, were performed. Pharmacophore screening was applied to predict the targets of oxymatrine and ulinastatin, and potential target genes shared by both cancer and sepsis were identified. Survival analysis was performed. The association between the target genes and tumor size and number of positive lymph nodes was investigated by Pearson correlation analysis. The association between the target genes and tumor stage was investigated by Fisher's exact test. Molecular docking analysis was performed to evaluate the affinity of the candidate drugs for their targets.
A total of 641 common genes were identified. GO enrichment analysis showed that common genes were enriched in neutrophil degranulation, inflammatory response and innate immune response. Reactome enrichment analysis showed that common genes were enriched in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, transcriptional regulation of granulopoiesis and interleukin-10 signaling. The PPI network showed that the top 10 core genes were TLR4, IL1B, IL10, ITGAM, TLR2, PTPRC, CDK1, FOS, MMP9 and ITGB2. The survival analysis showed that the high expression of BCAT1, CSAD, G6PD, GM2A, MMP9, PYGL and TOP2A was associated with poorer prognosis in several cancers. Molecular docking showed that oxymatrine and ulinastatin can bind to protein targets with highly stable binding.
We identified genes with common effects on both childhood sepsis and cancer, which provides new insights into the association between sepsis and cancer. In addition, two drugs with potential clinical application value were identified. Further studies are required to validate the role of these common core genes in sepsis and cancer and to evaluate the potential utility of these drugs.
脓毒症和癌症都是全球主要的死亡原因，它们具有一些共同的病理生理特征。一些研究表明脓毒症与癌症之间可能存在关联；然而，很少有研究调查这两种疾病共同涉及的核心基因。
使用儿科脓毒症数据集（GEO：GSE26378、GSE4607、GSE8121和GSE13904）和癌症数据库（TCGA：BRCA、COADREAD、ESCA、KIRC、LIHC、LUAD、STAD）确定脓毒症和癌症共有的核心基因。进行了基因本体（GO）和Reactome富集分析，以及蛋白质-蛋白质相互作用（PPI）网络分析。应用药效团筛选来预测氧化苦参碱和乌司他丁的靶点，并确定癌症和脓毒症共有的潜在靶基因。进行了生存分析。通过Pearson相关分析研究靶基因与肿瘤大小和阳性淋巴结数量之间的关联。通过Fisher精确检验研究靶基因与肿瘤分期之间的关联。进行分子对接分析以评估候选药物与其靶点的亲和力。
共鉴定出641个共同基因。GO富集分析表明，共同基因在中性粒细胞脱颗粒、炎症反应和先天免疫反应中富集。Reactome富集分析表明，共同基因在中性粒细胞脱颗粒、白细胞介素-4和白细胞介素-13信号传导、粒细胞生成的转录调控和白细胞介素-10信号传导中富集。PPI网络显示，前10个核心基因是TLR4、IL1B、IL10、ITGAM、TLR2、PTPRC、CDK1、FOS、MMP9和ITGB2。生存分析表明，BCAT1、CSAD、G6PD、GM2A、MMP9、PYGL和TOP2A的高表达与几种癌症的预后较差相关。分子对接表明，氧化苦参碱和乌司他丁可以与蛋白质靶点高度稳定地结合。
我们鉴定出了对儿童脓毒症和癌症均有共同影响的基因，这为脓毒症与癌症之间的关联提供了新的见解。此外，还鉴定出了两种具有潜在临床应用价值的药物。需要进一步研究来验证这些共同核心基因在脓毒症和癌症中的作用，并评估这些药物的潜在效用。
