Research on Differences and Immune Infiltration-Related Macrophages Between Non-Small Cell Lung Cancer and Adjacent Tissues

Non-Small Cell Lung Cancer (NSCLC) is a highly lethal respiratory tumor with unclear molecular mechanisms. RNA-seq data from 34 early-stage samples and adjacent non-cancerous tissues identified 1088 differentially expressed genes using Deseq2. Mendelian randomization (MR) analysis of 26,153 genes and 63,053 LUSC patients, including 7,838,805 SNPs, identified 213 potential exposure factors. Five differentially expressed genes (GYPE, PODXL2, RNF182, SIRPG, WNT7A) were identified, with PODXL2 as a risk factor. GO and KEGG analyses highlighted the mTOR and Wnt signaling pathways. Immune infiltration analysis showed decreased Plasma cells, Tregs, and activated Dendritic cells, but increased Macrophages M1. External validation using TCGA and 11 GEO datasets confirmed SIRPG's role in LUSC. SIRPG is a significant exposure risk factor for LUSC, with Macrophages M1 and the mTOR signaling pathway playing crucial roles.