The Oncogenic Role and Prognostic Value of PXDN in Human Stomach Adenocarcinoma

Abstract Stomach adenocarcinoma (STAD), recognized for its prevalence and poor prognostic profile, necessitates the urgent identification of novel therapeutic targets. Peroxidasin (PXDN), an enzyme with documented peroxidase activity, has been implicated in oncogenesis according to preceding research. However, its specific implications in STAD remain insufficiently characterized. In our investigation, we utilized public databases and clinical specimens to ascertain that PXDN expression is markedly elevated in STAD tissues and serves as an independent prognostic indicator for patient outcomes. Subsequently, our in vitro assays substantiated that PXDN silencing substantially attenuated proliferation, invasion and migration abilities in STAD. Mechanistically, we discovered that PXDN promote epithelial-mesenchymal transition and angiogenic capabilities in STAD cells, and may be regulated by the PI3K/AKT. Further scrutiny unveiled that PXDN levels influence the susceptibility of STAD cells to various chemotherapeutic and small molecule drugs. Moreover, we discerned a significant association between PXDN levels and the abundance of diverse immune cell types within STAD. Crucially, our study elucidated a profound linkage between PXDN level and the tumor immune microenvironment (TIM), proposing PXDN as a viable metric for evaluating the response to immune checkpoint inhibitors. Advancing beyond these findings, we found that PXDN exhibits significant associations with multiple immune checkpoints. In summary, our investigation suggested that PXDN plays critical roles in STAD and its levels could serve as a potential prognostic biomarker. Furthermore, targeting PXDN could offer an effective treatment strategy for STAD.