SCG2 Mediates HNSCC Progression With CCL2/TGFβ1 M2 Macrophage Infiltration.

Objectives: This study aims to unravel the mechanisms underlying M2 macrophage polarization in head and neck squamous cell carcinoma (HNSCC), and identify potential therapeutic targets.

Materials And Methods: We conducted an integrated bioinformatic analysis using HNSCC bulk transcriptomes from TCGA and GEO databases to pinpoint critical factors influencing M2 macrophage polarization and tumor prognosis. The significance of these genes was validated in function analysis, single-cell transcriptome datasets, and in vitro experiments. Their mechanisms in modulating M2 macrophage polarization were further explored by gene knockdown, cell coculture, and other assays for quantification.

Results: We identified a novel prognostic signature of five genes associated with M2 macrophage infiltration, in which SCG2 emerged as a pivotal factor in M2 macrophage polarization in HNSCC. High expression of SCG2 in tumor patients correlated with poorer prognoses, and knocking down SCG2 reduced the proliferation and migration of HNSCC cells, disrupting M2 macrophage polarization. Furthermore, interference of SCG2 resulted in a significant decrease in the secretion of pro-tumor cytokines such as CCL2 and TGFβ1.

Conclusions: Our findings provide deeper insights into the pathogenesis of HNSCC and offer promising therapeutic targets for HNSCC, especially SCG2, to inhibit M2 macrophage polarization and modulate cytokine secretion.