BackgroundEndocan, also known as endothelial cell specific molecule-1 (ESM1), is a 50kDa soluble proteoglycan which is frequently overexpressed in many cancer types. Whether it is dysregulated in head and neck squamous cell carcinoma (HNSCC) has not been investigated.MethodsWe analyzed the expression of ESM1 using bioinformatics analysis based on data from The Cancer Genome Atlas (TCGA), and then validated that ESM1 was significantly overexpressed in human HNSCC at the protein level using immunohistochemistry. We also analyzed the genes co-expressed with ESM1 in HNSCC.ResultsThe most correlated gene was angiopoietin-2 (ANGPT2), a molecule which regulates physiological and pathological angiogenesis. Several transcription factor binding motifs including SMAD3, SMAD4, SOX3, SOX4, HIF2A and AP-1 components were significantly enriched in the promoter regions of the genes co-expressed with ESM1. Further analysis based on ChIP-seq data from the ENCODE (Encyclopedia of DNA Elements) project revealed that AP-1 is an important regulator of ESM1 expression.ConclusionsOur results revealed a dysregulation of ESM1 and a potential regulatory mechanism for the co-expression network in HNSCC.