Significance of macrophage infiltration in the prognosis of lung adenocarcinoma patients evaluated by scRNA and bulkRNA analysis

Abstract

Purpose: To investigate the significance of macrophage infiltration to the prognosis of lung adenocarcinoma. Methods: R language bioinformatics analysis technology, was used to obtain macrophage infiltration-related module genes through WGCNA (Weighted Gene Co-Expression Network Analysis). Marker genes of macrophage subtypes were identified using single-cell sequencing of lung adenocarcinoma tissue. Risk score models were constructed and validated using external data cohorts and clinical samples. Results: Analysis of cohorts TCGA-LUAD, GSE11969, GSE31210, GSE50081, GSE72094 and GSE8894, revealed a negative correlation between macrophage infiltration and survival. Immunohistochemical analyses of clinical samples were consistent with these data. Based on cell-cluster-markers and TAMs-related-genes, TOP8 genes were obtained (C1QTNF6, CCNB1, FSCN1, HMMR, KPNA2, PRC1, RRM2, and TK1) with a significant association to prognosis. Risk score models including 9 factors (C1QTNF6, FSCN1, KPNA2, GLI2, TYMS, BIRC3, RBBP7, KRT8, GPR65) for prognosis were constructed. The efficacy, stability and generalizability of the risk score models were validated using multiple data cohorts (GSE19188, GSE26939, GSE31210, GSE50081, GSE42127, and GSE72094). Conclusions: Macrophage infiltration negatively correlates with prognosis in patients with lung adenocarcinoma. Based on cell-cluster-markers and TAMs-related-genes, both TOP8 genes (C1QTNF6, CCNB1, FSCN1, HMMR, KPNA2, PRC1, RRM2, TK1) and risk score models using C1QTNF6, FSCN1, KPNA2, GLI2, TYMS, BIRC3, RBBP7, KRT8, GPR65 could predict disease prognosis.