Zhou Yunxuan, Geng Shijin, Tang Rong-Chun, Yu Hengxiang, Zhang Ao, Bai Yuekui, Zhang Jun
Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Research on Major Immunology-Related Diseases, Peking University, Beijing, China.
General Surgery, Haidian Hospital, Beijing, China.
Sci Rep. 2025 Mar 11;15(1):8392. doi: 10.1038/s41598-025-91386-1.
Spermatogenesis-associated protein 2 (SPATA2) is primarily named for its important role in spermatogenesis. Its function in tumorigenesis remains elusive. Here, we used various bioinformatic tools to systematically analyze the expression patterns of SPATA2 in cancers, the correlation of SPATA2 expression with clinical parameters, genetic variation, methylation, phosphorylation, immune infiltration and immune therapy. SPATA2 is significantly upregulated in multiple cancers and its expression was associated with tumor stage, grade and serve as a potential prognostic marker in LIHC. Notably, SPATA2 was also linked to immune suppression, exhibiting positive correlations with immune checkpoint genes and immune suppressive cells such as regulatory T cells and MDSCs. Furthermore, SPATA2 interacted and co-expressed with proteins involved in DNA repair mechanisms, indicating its potential role in maintaining genomic stability. Finally, we conducted biological experiments to investigate the role of SPATA2 in LIHC. SPATA2 knockdown enhances the migration and proliferation capabilities of Hep-G2 and HuH7 cell lines. These findings underscore the significance of SPATA2 in cancer biology, suggests its role in both the tumor microenvironment and the tumor cell level and its potential as a prognostic marker and therapeutic target in oncology, particularly in LIHC.
精子发生相关蛋白2（SPATA2）主要因其在精子发生中的重要作用而得名。其在肿瘤发生中的功能仍不清楚。在此，我们使用了各种生物信息学工具，系统地分析了SPATA2在癌症中的表达模式、SPATA2表达与临床参数、基因变异、甲基化、磷酸化、免疫浸润和免疫治疗的相关性。SPATA2在多种癌症中显著上调，其表达与肿瘤分期、分级相关，并在肝癌中作为潜在的预后标志物。值得注意的是，SPATA2还与免疫抑制有关，与免疫检查点基因以及调节性T细胞和骨髓来源的抑制细胞等免疫抑制细胞呈正相关。此外，SPATA2与参与DNA修复机制的蛋白质相互作用并共同表达，表明其在维持基因组稳定性方面的潜在作用。最后，我们进行了生物学实验，以研究SPATA2在肝癌中的作用。敲低SPATA2可增强Hep-G2和HuH7细胞系的迁移和增殖能力。这些发现强调了SPATA2在癌症生物学中的重要性，表明其在肿瘤微环境和肿瘤细胞水平上的作用以及作为肿瘤学中预后标志物和治疗靶点的潜力，特别是在肝癌中。
