GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE343nnn/GSE343350/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE343nnn/GSE343350/suppl/GSE343350_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE343nnn/GSE343350/primary200OKOtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE343350GEOGSEfalseMulti-tissue gene expression in HNSCCThe molecular mechanisms in the development of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remain poorly understood. Previous studies suggest molecular overlap between head and neck SCC (HNSCC) and lung SCC. In this study, we investigated whether lung cancer-associated genes are enriched among differentially expressed genes during stepwise LHSCC development. Spatial transcriptomic profiling using the Xenium platform (10x Genomics) was performed on formalin-fixed paraffin embedded tissue of normal mucosa, low-grade dysplasia (LG-Dys), high-grade dysplasia/carcinoma in situ (HG-Dys/CIS) and invasive carcinoma from eleven patients. Over 40 differentially expressed genes were identified, grouped into key biological processes, including transport, immune modulation, epithelial integrity, signaling and metabolism. Gene expression patterns segregated lesions into two molecular groups, whereby LG-Dys resembled normal mucosa, while HG-Dys aligned with CIS. Six genes (CCDC39, DNAAF1, GDF15, GKN2, RGS16 and TSPAN19) were consistently altered between HG-Dys/CIS and invasive carcinoma, highlighting them as potential biomarkers of malignant transformation. Additionally, EPCAM and SERPINB3 showed altered expression in LHSCC development, consistent with previous studies in other epithelial malignancies. These findings further support similar genetic pathways involved in lung cancer and LHSCC development. Furthermore, our results revealed novel molecular events underlying LHSCC development and identified candidate biomarkers of early invasiveness.2026/08/16GSE343350GSM9949643GSM994964233762343350Homo sapiens