Multi-omic profiling unveils molecular landscapes and heterogeneous tumor microenvironment in sinonasal squamous cell carcinoma [Bulk RNA-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.