Pan‐cancer analysis: SPAG5 is an immunological and prognostic biomarker for multiple cancers

• Published in: The FASEB journal 2023-10, Vol.37 (10), p.e23159-n/a
• Main Authors: Gao, Xiaofeng, Bu, Huitong, Gao, Xuzheng, Wang, Ying, Wang, Long, Zhang, Zhenwang
• Format: Article
• Language: English
• Subjects: diagnosis; immunotherapy; pan‐cancer; SPAG5; tumor immune microenvironment
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.202300626R

Sperm‐associated antigen 5 (SPAG5) is a mitotic spindle protein that regulates the separation of sister chromatids into daughter cells. Recent studies have discovered its overexpression in various cancers, suggesting its oncogenic characteristics and functions. However, a comprehensive analysis of SPAG5 regarding its diagnostic, prognostic, and immune‐related effects across different cancer types is lacking. In this study, we employed bioinformatics methods and integrated multiple public databases to explore the potential oncogenic role of SPAG5. We analyzed its expression, prognosis, related chemicals, enriched pathways, immune infiltration, and its impact on different tumor genetic alterations. The results revealed that SPAG5 is highly expressed in most cancers and significantly correlates with poor patient prognosis. Additionally, SPAG5 expression showed potential for early cancer diagnosis in 15 different cancer types. In terms of tumor immunity, high expression of SPAG5 was associated with an immunosuppressive tumor microenvironment and immune therapy efficacy indicators. SPAG5 expression exhibited a negative correlation with most immune cell infiltrates but demonstrated a significant positive correlation with Th2 cells and MDSC cells. Multicolor fluorescence immunohistochemistry demonstrated that SPAG5 activates immune cell populations within tumors, indicating its significant role in the tumor microenvironment. Enrichment analysis indicated that SPAG5‐related genes are mainly involved in cell cycle, cellular senescence, P53 signaling pathway, and FoxO signaling pathway. Furthermore, we confirmed the high expression of SPAG5 in cancer cells and observed that its knockdown upregulated the expression of the p53 protein. In conclusion, SPAG5 holds value as a diagnostic, prognostic, and immune biomarker in various cancers and may provide a novel target for tumor immunotherapy. The summary diagram of the mechanism of action of SPAG5 in cancer. In tumor cells, SPAG5 regulates immune cell population and participates in tumor microenvironment. SPAG5 is mainly involved in cell cycle, cell aging, P53 signaling pathway, and FoxO signaling pathway, which has diagnostic, prognostic, and immune biomarker value in various cancers, and may provide a new target for tumor immunotherapy.