Yu -Chun Li ^1* Yan-Hong Xiao ^1* Fei-Xiong Chen ^1* Si-Yu Xiao ^1* Jian-Mei Lin ^1* Shu- Tao Cai ^1* Cui-Lan Zeng ^1* Xue-Yan Ye ^1* Xu-Fa Yu ^1* Li Yuan ^2* Shi-Bing Li ^1,3*

• ¹ Department of Clinical Laboratory, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
• ² Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, Guangdong Province, China
• ³ Sun Yat-sen University, Guangzhou, China

Background: Investigating the oncogenes and mechanisms in driving oncogenic processes in human tumors is imperative for the development of efficient therapies. Peroxidasin (PXDN) has been reported to play a critical role in tissue development and homeostasis. However, the function of PXDN in the occurrence and development of Nasopharyngeal Carcinoma (NPC) is still unknown. Methods: Data from multiple databases such as GEO and TCGA were utilized to analyze the expression levels of PXDN. Taking nasopharyngeal carcinoma as an example, in vitro experiments were conducted to explore the biological functions of PXDN. Overexpression stable cell lines were obtained through lentiviral infection, cell proliferation was examined using CCK8 and BrdU incorporation assays, and clone formation experiments were performed to assess cell growth. Transwell and wound healing assays were employed to evaluate cell invasion and migration abilities. Additionally, immunofluorescence staining with multiple targets was used to analyze the immune microenvironment of tumor tissues. Co-culture experiments followed by clone formation and CFSE incorporation assays were conducted to observe the impact of NPC stable cell lines on T cells. Flow cytometry was performed to detect the surface marker and the cytokine of T cells after co-culture to assess T cell function. Results: PXDN is highly expressed in multiple tumors, its high expression and mutation profile are correlated with poorer survival. Functionally, PXDN plays a crucial role in promoting oncogenic processes by enhancing cell proliferation and metastasis ability in NPC. Mechanistically, PXDN activates extracellular matrix (ECM) signaling pathways while simultaneously inhibiting T cell infiltration and activation, thereby facilitating cancer progression. Conclusion: we characterized PXDN as a valuable biomarker for pancancer diagnosis and prognosis. We also uncovered new oncogenic roles of PXDN in promoting cancer progression and regulating T cell immunosuppressive function in NPC.