show Abstracthide AbstractMore than 90% of cancer cases in head and neck region are oral squamous cell carcinoma. Recent studies identified several tumor-specific metabolites for the screening or diagnosis of OSCC patients. However, the metabolic reprogramming of OSCC is not well understood. Here, we compared the metabolites between cancerous and paracancerous tissues of OSCC patients and investigated the metabolism of ?-aminobutyrate in OSCC derived cells. Our data revealed that the increase of ?-aminobutyrate was promoted by the synthesis of glutamate beyond the mitochondria, which was regulated by glutamine synthetase. This study is not only benefit for understanding the pathological mechanisms of OSCC, but also has application prospects for the diagnosis and therapy of OSCC. Overall design: Comparative gene expression profiling analysis of RNA-seq data for CA-13 cells and PA-35 cells.