Identification of hub genes correlated with tumor-associated M1-like macrophage infiltration in soft tissue sarcomas.

ABSTRACT

Soft tissue sarcomas (STS) are a heterogeneous series of tumors that might result in severe disability and death. Tumor-associated M1-like macrophage infiltration plays a critical role in tumor development and progression. This study aimed at identifying the hub genes associated with M1-like macrophage infiltration in STS cells. First, the expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were imported to calculate the level of M1-like macrophage infiltration by CIBERSORTx. Afterward, the Kaplan-Meier survival analysis was performed to evaluate the correlation between macrophage infiltration and prognosis. Then, weighted gene co-expression network analysis (WGCNA) and protein-protein interaction analysis of GEO data were applied to identify the key gene related to M1-like macrophage infiltration, followed by the functional analysis using TCGA cohort to validate downstream signaling associated with the gene. Finally, pan-cancer analysis was conducted to investigate the gene function in other types of tumors. We found LCK expression positively related to the M1-like macrophage infiltration level, and it positively regulated the expression level of genes regulated to macrophage polarization, and chemotaxis, including interferon-γ (INF-γ), interleukin-12 (IL12), tumor necrosis factor (TNF), PI3K, NF-κB, and CXCL9, 10, and 11. In summary, an 'LCK-INF-γ/IL-12-TNF/PI3K-NF-κB' axis might exist in STS cells that regulate M1-like macrophage infiltration.