Uncovering S100A11, CYBA, MYL6, and FCGRT as macrophage-associated diagnostic markers for non-small cell lung cancer

: Macrophages in the tumor microenvironment (TME) are closely relevant to the growth of non-small cell lung cancer (NSCLC). Exploring their related biomarkers can help reveal the mechanisms underlying the development of NSCLC. We downloaded single-cell and transcriptomic data from GEO. scRNA-Seq was applied to analyze macrophage subpopulation infiltration; hdWGCNA was utilized to screen the hub genes. LASSO and SVM-RFE machine learning algorithms were further used to identify macrophage-related NSCLC progression biomarkers. Moreover, ROC curves were plotted to evaluate diagnostic performance; hTFtarget database was accessed to predict the putative transcription factors. CCK-8, Transwell, and scratch healing tests were performed to validate biomarkers’ regulatory roles in NSCLC cell malignant phenotypes. Eight NSCLC cell subpopulations were identified. Hub genes linked to macrophages were enriched in tumor immune regulation. Biomarkers S100A11, CYBA, MYL6, and FCGRT showed potential diagnostic performance in the discovery dataset and retained favorable diagnostic performance in the independent GSE19188 validation cohort. S100A11 silencing inhibited NSCLC cell proliferation, migration, and invasion. This study identified macrophage-associated genes related to NSCLC progression as potential biomarkers and preliminarily evaluated their diagnostic performance. The present findings provide preliminary references for the identification of macrophage-associated diagnostic biomarkers in NSCLC.