Abstract
Salivary duct carcinoma (SDC) is a rare and aggressive malignant tumor, with scarce reports on its pathogenesis and treatment methods. This study aims to explore the potential biomarkers of SDC. SDC cases were analyzed using Illumina microarrays, and Limma identified differentially expressed genes (DEGs) between cancer and normal tissues. An intersection of these DEGs with the differential genes from the GSE138581 dataset was obtained through Venn analysis to identify the core DEGs. The core DEGs were analyzed by search Tool for the retrieval of interacting genes/proteins (STRING) and cytoscape to identify the genes most related to the disease in SDC patients. Core genes were enriched with gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG); their pan-cancer implications and immune aspects were studied. Finally, the core DEGs were initially validated by immunohistochemistry in SDC samples. Fifty DEGs were found by exome sequencing, 3158 by the GSE138581 microarray. Thirteen common genes were identified by Venn analysis, and ten core genes, including Forkhead box M1 (FOXM1), collagen, type XI, alpha 1 (COL11A1), and neuron navigator 2 (NAV2), were selected. GO enrichment of core genes included positive regulation of calcium ion transport and ATPase activity, and KEGG analysis focused on related pathways. Expression was evaluated across 34 cancers from the TCGA database, and immune DEG Phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) was identified. The obtained DEGs were further validated by immunohistochemistry (IHC). Identifying the DEGs not only helps improve our understanding of SDC pathogenesis but also promises to identify potential biomarkers and new therapeutic targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-35239-5.