Chen Qingyong, Wang Dongqing, Chen Zhipeng, Lin Liqiang, Shao Qiang, Zhang Han, Li Peng, Lv Huaiqing
The Second School of Clinical Medicine of Binzhou Medical University, Yan Tai, China.
Department of Otorhinolaryngology, Linyi People's Hospital, Linyi, China.
Heliyon. 2024 Sep 10;10(18):e37738. doi: 10.1016/j.heliyon.2024.e37738. eCollection 2024 Sep 30.
To analyze and validate differential genes in the cytokine-cytokine receptor interaction CCRI pathway in laryngeal squamous cell carcinoma (LSCC) using bioinformatics and Mendelian randomization (MR) to find potential biomarkers for LSCC.
Five sets of LSCC-related gene chips were downloaded from the GEO database, and four sets of combined datasets were randomly selected as the test set and one set as the validation set to screen for differential genes in the CCRI pathway; two-way Mendelian randomization was performed to analyze the causal relationship between cytokine receptor as the exposure factor and LSCC as the outcome variable; and the causal relationship was analyzed by DGIdb, Miranda, miRDB, miRWalk, TargetScan, spongeScan, and TISIDB databases to analyze the relationship between differential genes and drugs, immune cell infiltration, and mRNA-miNA-lncRNA interactions.
A total of 7 differentially expressed genes CD27, CXCL2, CXCL9, INHBA, IL6, CXCL11, and TNFRSF17 were screened for enrichment in the CCRI signaling pathway; MR analysis showed that the CCRI receptor was a risk factor for LSCC (IVW: OR = 1.629, 95 % CI:1.060-2.504, P = 0.026); Seven differential genes were correlated with drugs, immune cells and mRNA-miNA-lncRNA, respectively; the CCRI differential gene expression analysis in the validation set was consistent with the test set results.
This study provided CCRI differential gene expression by bioinformatics, and MR analysis demonstrated that cytokine receptors are risk factors for LSCC, providing new ideas for the pathogenesis and therapeutic targets of LSCC.
利用生物信息学和孟德尔随机化(MR)分析并验证喉鳞状细胞癌(LSCC)中细胞因子-细胞因子受体相互作用(CCRI)途径中的差异基因,以寻找LSCC的潜在生物标志物。
从GEO数据库下载五组LSCC相关基因芯片,随机选择四组合并数据集作为测试集,一组作为验证集,筛选CCRI途径中的差异基因;进行双向孟德尔随机化分析以细胞因子受体为暴露因素与LSCC为结局变量之间的因果关系;通过DGIdb、Miranda、miRDB、miRWalk、TargetScan、spongeScan和TISIDB数据库分析因果关系,以分析差异基因与药物、免疫细胞浸润和mRNA-miNA-lncRNA相互作用之间的关系。
共筛选出7个差异表达基因CD27、CXCL2、CXCL9、INHBA、IL6、CXCL11和TNFRSF17,在CCRI信号通路中富集;MR分析显示CCRI受体是LSCC的危险因素(IVW:OR = 1.629,95%CI:1.060 - 2.504,P = 0.026);7个差异基因分别与药物、免疫细胞和mRNA-miNA-lncRNA相关;验证集中CCRI差异基因表达分析与测试集结果一致。
本研究通过生物信息学提供了CCRI差异基因表达,MR分析表明细胞因子受体是LSCC的危险因素,为LSCC的发病机制和治疗靶点提供了新思路。