Abstract
Accurate metabolic biomarkers are still scarce and essential for prognosis of lung cancer progression and prognosis. Previous studies have found that two metabolites including taurine and proline are abnormally elevated in lung cancer patients with different stages. This study aimed to elucidate their functional role in lung cancer progression, providing valuable insights into potential therapeutic targets for intervention. Taurine and proline could promote lung tumour growth for the first time, suggesting poor prognosis for lung cancer progression. In transcriptome analysis, both taurine and proline down-regulated the expression of gene Zinc-α2-glycoprotein (Azgp1). Azgp1, down-regulated in lung cancer patients, was significantly associated with key targets of the taurine and proline metabolic pathways. Azgp1 could also significantly affect downstream lipid metabolic pathways in lung cancer. In metabolome analysis, taurine and proline could alter lipid metabolism mediated by mammalian target of rapamycin (mTOR). Moreover, taurine and proline were found to be able to suppress Azgp1 expression and activate mTOR expression. Overexpression of Azgp1, in turn, significantly inhibited lung cancer progression, accompanied by the inhibition of mTOR expression. These results suggested a pro-cancer role of both taurine and proline in lung cancer and identified the Azgp1/mTOR axis as an under-reported pathway involving lung cancer progression.