New understanding of SPAG4 as a tumor marker: SPAG4 is a potential pan-cancer biomarker for prognosis and immunotherapy

Abstract Human sperm-associated antigen 4 (SPAG4), as a member of the cancer-testis antigen family , is considered to be a potential cancer marker. However, it is still unknown about the pathogenic role of SPAG4 in various cancers and whether SPAG4 acts through certain common molecular mechanisms in the immuno-oncological context of the tumor microenvironment, prognosis, and therapeutic response. Here, we explored the oncogenic role of SPAG4 in 33 human tumors based on TCGA and GEO databases using web-based tools such as TIMER2.0, GEPIA2, GSCA, TIDE, and Western Blot experiments. The results showed that SPAG4 was highly expressed in most tumor tissues and predicted a poor clinical prognosis. In addition, SPAG4 may be involved in tumorigenesis and development by affecting the activities of certain kinases on pathways such as FoxO and P53. Moreover, SPAG4 has an important role in the tumor microenvironment and is likely to be involved in the regulation of the immune microenvironment. Most importantly, SPAG4 expression was significantly associated with drug resistance and immune checkpoint blockade therapy in tumor patients, and could potentially mediate the occurrence of immune escape. In conclusion, our study strongly suggests that SPAG4 is an immune oncogenic molecule that can be used as a biomarker for cancer detection, prognosis, treatment design, and follow-up.