■肺鳞状细胞癌(LUSC)是一种严重且高致死性的呼吸系统恶性肿瘤,它在分子水平上的分子机制仍然不清楚。
■我们从从3个不同中心的早期LUSC和邻近非癌组织获得的8个手术样本中获得了RNA-seq数据。利用Deseq2,我们鉴定了1088个差异表达基因,其|LogFC|>1和p值<0.05阈值。此外,通过对26,153个基因和63,053个LUSC患者的暴露数据进行MR分析,纳入7,838,805个SNP作为端点,我们确定了213个基因是潜在的暴露因子.
■结果相交后,我们确定了5个差异表达基因,包括GYPE,PODXL2,RNF182,SIRPG,WNT7APODXL2(OR95%CI,1.169(1.040至1.313))被确定为暴露风险因素,在逆方差加权模型下,p值小于0.01。GO和KEGG分析显示泛素-蛋白转移酶活性增强和诸如mTOR信号通路和Wnt信号通路等通路的激活。免疫浸润分析显示浆细胞下调,调节性T细胞(Tregs),和由鉴定的基因集激活的树突状细胞,而在巨噬细胞M1中观察到增强。此外,我们使用TCGA数据库的RNA-seq数据和LUSC的11个GEO数据集外部验证了这5个基因的表达水平,结果表明,SIRPG可以诱导LUSC。
■SIRPG成为LUSC值得注意的暴露风险因素。免疫浸润分析强调巨噬细胞M1和mTOR信号通路在LUSC中起重要作用。
UNASSIGNED: Squamous cell carcinoma of the lung (LUSC) is a severe and highly lethal malignant tumor of the respiratory system, and its molecular mechanisms at the molecular level remain unc\\lear.
UNASSIGNED: We acquired RNA-seq data from 8 surgical samples obtained from early-stage LUSC and adjacent non-cancerous tissues from 3 different centers. Utilizing Deseq2, we identified 1088 differentially expressed genes with |LogFC| > 1 and a p-value < 0.05 threshold. Furthermore, through MR analysis of Exposure Data for 26,153 Genes and 63,053 LUSC Patients, incorporating 7,838,805 SNPs as endpoints, we identified 213 genes as potential exposure factors.
UNASSIGNED: After intersecting the results, we identified 5 differentially expressed genes, including GYPE, PODXL2, RNF182, SIRPG, and WNT7A. PODXL2 (OR 95% CI, 1.169 (1.040 to 1.313)) was identified as an exposed risk factor, with p-values less than 0.01 under the inverse variance weighted model. GO and KEGG analyses revealed enhanced ubiquitin-protein transferase activity and activation of pathways such as the mTOR signaling pathway and Wnt signaling pathway. Immune infiltration analysis showed downregulation of Plasma cells, T cells regulatory (Tregs), and Dendritic cells activated by the identified gene set, while an enhancement was observed in Macrophages M1. Furthermore, we externally validated the expression levels of these five genes using RNA-seq data from TCGA database and 11 GEO datasets of LUSC, and the results showed SIRPG could induce LUSC.
UNASSIGNED: SIRPG emerged as a noteworthy exposure risk factor for LUSC. Immune infiltration analysis highlighted Macrophages M1 and mTOR signaling pathway play an important role in LUSC.