Multi-omic profiling unveils molecular landscapes and heterogeneous tumor microenvironment in sinonasal squamous cell carcinoma [RPMI 2650 bulk ATAC-seq]
Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy with limited treatment options. Here, we conduct a comprehensive multi-omic analysis, integrating bulk and single-cell transcriptomics, epigenomics, and DNA methylation profiling. Our study identifies distinct gene signatures, cellular compositions, and regulatory mechanisms that drive SNSCC pathogenesis. Epigenetic alterations reveal a regulatory landscape underlying transcriptional changes, and we characterize heterogeneous tumor cell populations with unique molecular profiles. Hypoxia-related cells emerge as key drivers of angiogenesis and disease progression. Notably, we uncover a critical interaction between hypoxic tumor cells and endothelial tip cells, mediated by factors such as adrenomedullin (ADM), highlighting a pivotal mechanism in tumor development. These findings provide valuable insights into the tumor microenvironment (TME) of SNSCC and suggest potential therapeutic targets to improve treatment strategies for this challenging malignancy. Overall design: Bulk ATAC-seq was performed on RPMI 2650 cells exposed for 24 hours to either normoxia or hypoxia (1% O2).