Clinical and Functional Significance of SPATA2 in Cancer Particularly in LIHC

Overview

Journal Sci Rep

Specialty Science

Date 2025 Mar 12

PMID 40069269

Authors

Yunxuan Zhou

Shijin Geng

Rong-Chun Tang

Hengxiang Yu

Ao Zhang

Yuekui Bai

Jun Zhang

Affiliations

Soon will be listed here.

Abstract

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.

References

Savage K, Harkin D . BRCA1, a 'complex' protein involved in the maintenance of genomic stability. FEBS J. 2014; 282(4):630-46. DOI: 10.1111/febs.13150. View

Milne R, Antoniou A . Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers. Ann Oncol. 2011; 22 Suppl 1:i11-7. DOI: 10.1093/annonc/mdq660. View

Masola V, Greco N, Tozzo P, Caenazzo L, Onisto M . The role of SPATA2 in TNF signaling, cancer, and spermatogenesis. Cell Death Dis. 2022; 13(11):977. PMC: 9675801. DOI: 10.1038/s41419-022-05432-1. View

Huang R, Zhou P . DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy. Signal Transduct Target Ther. 2021; 6(1):254. PMC: 8266832. DOI: 10.1038/s41392-021-00648-7. View

Hornbeck P, Chabra I, Kornhauser J, Skrzypek E, Zhang B . PhosphoSite: A bioinformatics resource dedicated to physiological protein phosphorylation. Proteomics. 2004; 4(6):1551-61. DOI: 10.1002/pmic.200300772. View

Tang Z, Kang B, Li C, Chen T, Zhang Z . GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019; 47(W1):W556-W560. PMC: 6602440. DOI: 10.1093/nar/gkz430. View

Tan T, Zybina Y, McKenna C, Olow A, Rukmini S, Wong M . SPATA2 and CYLD inhibit T cell infiltration into colorectal cancer regulation of IFN-γ/STAT1 axis. Front Oncol. 2022; 12:1016307. PMC: 9756846. DOI: 10.3389/fonc.2022.1016307. View

Ren Y, Jiang J, Jiang W, Zhou X, Lu W, Wang J . Spata2 Knockdown Exacerbates Brain Inflammation via NF-κB/P38MAPK Signaling and NLRP3 Inflammasome Activation in Cerebral Ischemia/Reperfusion Rats. Neurochem Res. 2021; 46(9):2262-2275. DOI: 10.1007/s11064-021-03360-8. View

Balkwill F . TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev. 2006; 25(3):409-16. DOI: 10.1007/s10555-006-9005-3. View

10.

Onisto M, Slongo L, Graziotto R, Zotti L, Negro A, Merico M . Evidence for FSH-dependent upregulation of SPATA2 (spermatogenesis-associated protein 2). Biochem Biophys Res Commun. 2001; 283(1):86-92. DOI: 10.1006/bbrc.2001.4754. View

11.

Wagner S, Satpathy S, Beli P, Choudhary C . SPATA2 links CYLD to the TNF-α receptor signaling complex and modulates the receptor signaling outcomes. EMBO J. 2016; 35(17):1868-84. PMC: 5007551. DOI: 10.15252/embj.201694300. View

12.

Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q . TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020; 48(W1):W509-W514. PMC: 7319575. DOI: 10.1093/nar/gkaa407. View

13.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

14.

Coleman R, Oza A, Lorusso D, Aghajanian C, Oaknin A, Dean A . Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 390(10106):1949-1961. PMC: 5901715. DOI: 10.1016/S0140-6736(17)32440-6. View

15.

Fahey M, Bennett M, Mahon C, Jager S, Pache L, Kumar D . GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data. BMC Bioinformatics. 2011; 12:298. PMC: 3213248. DOI: 10.1186/1471-2105-12-298. View

16.

Ji H, Zhang L, Zou M, Sun Y, Dong X, Mi Z . SPATA2 suppresses epithelial-mesenchymal transition to inhibit metastasis and radiotherapy sensitivity in non-small cell lung cancer via impairing DVL1/β-catenin signaling. Thorac Cancer. 2023; 14(11):969-982. PMC: 10101837. DOI: 10.1111/1759-7714.14828. View

17.

Schlicher L, Wissler M, Preiss F, Brauns-Schubert P, Jakob C, Dumit V . SPATA2 promotes CYLD activity and regulates TNF-induced NF-κB signaling and cell death. EMBO Rep. 2016; 17(10):1485-1497. PMC: 5048381. DOI: 10.15252/embr.201642592. View

18.

Ling T, Yu F, Cao H . miR-182 controls cell growth in gastrointestinal stromal tumors by negatively regulating CYLD expression. Oncol Rep. 2018; 40(6):3705-3713. DOI: 10.3892/or.2018.6765. View

19.

Chandrashekar D, Bashel B, Balasubramanya S, Creighton C, Ponce-Rodriguez I, Chakravarthi B . UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017; 19(8):649-658. PMC: 5516091. DOI: 10.1016/j.neo.2017.05.002. View

20.

Graziotto R, Foresta C, Scannapieco P, Zeilante P, Russo A, Negro A . cDNA cloning and characterization of PD1: a novel human testicular protein with different expressions in various testiculopathies. Exp Cell Res. 1999; 248(2):620-6. DOI: 10.1006/excr.1999.4449. View