Comprehensive Analysis of Selenoprotein Gene Expression and Prognostic Value in Ovarian Cancer

Overview

Journal Turk J Obstet Gynecol

Specialty Gynecology & Obstetrics

Date 2024 Dec 12

PMID 39663776

Authors

Yingying Hou

Hongye Shen

Honghua Dong

Affiliations

Soon will be listed here.

Abstract

Objective: To comprehensively analyze the expression and prognostic value of selenoprotein in ovarian cancer (OV).

Materials And Methods: GEPIA and cBioPortal were used to analyze selenoprotein expression and mutations and copy number variations. Kaplan-Meier plotter and the tumor immune estimation resource were used to evaluate the impact of these genes on clinical prognosis and their correlation with tumor immune infiltration.

Results: Compared with normal tissues, the expression of iodothyronine deiodinase 3 (DIO3), glutathione peroxidase 4, SECISBP2, SELM, and SELP was decreased in the four gynecological malignancies. In OV, selenoprotein had the highest number of mutations (309) and mutation frequency (52.91%), whereas the lowest was observed in endometrial cancer (29.72%). DIO3, selenoprotein O (SELO), and selenoprotein T (SELT) are significantly related to the prognosis of OV. Immune infiltration analysis showed that DIO3 was associated with tumor-associated macrophages, SELO with CD4+ T-cells and monocytes, and SELT with T-cells. Enrichment analysis revealed that DIO3 is mainly involved in inflammatory immune responses and the Ras signaling pathway, SELO is primarily related to innate immune responses, and SELT is closely associated with mitochondrial oxidative phosphorylation.

Conclusion: This study explored the expression characteristics of 25 selenoprotein in patients with gynecological malignancies and found that DIO3, SELO, and SELT were significantly associated with the prognosis and clinical features of OV, which are potential therapeutic targets.

References

Glazov E, McWilliam S, Barris W, Dalrymple B . Origin, evolution, and biological role of miRNA cluster in DLK-DIO3 genomic region in placental mammals. Mol Biol Evol. 2008; 25(5):939-48. DOI: 10.1093/molbev/msn045. View

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

Groeneveld S, Faget J, Zangger N, Meylan E . Snail mediates repression of the Dlk1-Dio3 locus in lung tumor-infiltrating immune cells. Oncotarget. 2018; 9(64):32331-32345. PMC: 6122344. DOI: 10.18632/oncotarget.25965. View

Liao Y, Wang J, Jaehnig E, Shi Z, Zhang B . WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 2019; 47(W1):W199-W205. PMC: 6602449. DOI: 10.1093/nar/gkz401. View

Moskovich D, Alfandari A, Finkelshtein Y, Weisz A, Katzav A, Kidron D . DIO3, the thyroid hormone inactivating enzyme, promotes tumorigenesis and metabolic reprogramming in high grade serous ovarian cancer. Cancer Lett. 2020; 501:224-233. DOI: 10.1016/j.canlet.2020.11.011. View

Song M, Kumaran M, Gounder M, Gibbon D, Nieves-Neira W, Vaidya A . Phase I trial of selenium plus chemotherapy in gynecologic cancers. Gynecol Oncol. 2018; 150(3):478-486. PMC: 6154492. DOI: 10.1016/j.ygyno.2018.07.001. View

Sundstrom H, Ylikorkala O, Kauppila A . Serum selenium and thromboxane in patients with gynaecological cancer. Carcinogenesis. 1986; 7(7):1051-2. DOI: 10.1093/carcin/7.7.1051. View

Sreelatha A, Yee S, Lopez V, Park B, Kinch L, Pilch S . Protein AMPylation by an Evolutionarily Conserved Pseudokinase. Cell. 2018; 175(3):809-821.e19. PMC: 6524645. DOI: 10.1016/j.cell.2018.08.046. View

Dai R, Lu R, Ahmed S . The Upregulation of Genomic Imprinted DLK1-Dio3 miRNAs in Murine Lupus Is Associated with Global DNA Hypomethylation. PLoS One. 2016; 11(4):e0153509. PMC: 4829153. DOI: 10.1371/journal.pone.0153509. View

10.

Zhou Z, Li W, Zhang F, Hu K . The value of squamous cell carcinoma antigen (SCCa) to determine the lymph nodal metastasis in cervical cancer: A meta-analysis and literature review. PLoS One. 2017; 12(12):e0186165. PMC: 5724822. DOI: 10.1371/journal.pone.0186165. View

11.

Pothion H, Jehan C, Tostivint H, Cartier D, Bucharles C, Falluel-Morel A . Selenoprotein T: An Essential Oxidoreductase Serving as a Guardian of Endoplasmic Reticulum Homeostasis. Antioxid Redox Signal. 2020; 33(17):1257-1275. DOI: 10.1089/ars.2019.7931. View

12.

Gao J, Aksoy B, Dogrusoz U, Dresdner G, Gross B, Sumer S . Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6(269):pl1. PMC: 4160307. DOI: 10.1126/scisignal.2004088. View

13.

Moskovich D, Finkelshtein Y, Alfandari A, Rosemarin A, Lifschytz T, Weisz A . Targeting the DIO3 enzyme using first-in-class inhibitors effectively suppresses tumor growth: a new paradigm in ovarian cancer treatment. Oncogene. 2021; 40(44):6248-6257. DOI: 10.1038/s41388-021-02020-z. View

14.

Lanczky A, Gyorffy B . Web-Based Survival Analysis Tool Tailored for Medical Research (KMplot): Development and Implementation. J Med Internet Res. 2021; 23(7):e27633. PMC: 8367126. DOI: 10.2196/27633. View

15.

Luongo C, Dentice M, Salvatore D . Deiodinases and their intricate role in thyroid hormone homeostasis. Nat Rev Endocrinol. 2019; 15(8):479-488. DOI: 10.1038/s41574-019-0218-2. View

16.

Al-Harbi S, Choudhary G, Ebron J, Hill B, Vivekanathan N, Ting A . miR-377-dependent BCL-xL regulation drives chemotherapeutic resistance in B-cell lymphoid malignancies. Mol Cancer. 2015; 14:185. PMC: 4632834. DOI: 10.1186/s12943-015-0460-8. View

17.

Han S, Lee B, Yim S, Gladyshev V, Lee S . Characterization of mammalian selenoprotein o: a redox-active mitochondrial protein. PLoS One. 2014; 9(4):e95518. PMC: 3994087. DOI: 10.1371/journal.pone.0095518. View

18.

Muecke R, Schomburg L, Glatzel M, Berndt-Skorka R, Baaske D, Reichl B . Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology. Int J Radiat Oncol Biol Phys. 2010; 78(3):828-35. DOI: 10.1016/j.ijrobp.2009.08.013. View

19.

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

20.

Zhuang W, Liu J, Li W . hsa-miR-33-5p as a Therapeutic Target Promotes Apoptosis of Breast Cancer Cells Selenoprotein T. Front Med (Lausanne). 2021; 8:651473. PMC: 8110722. DOI: 10.3389/fmed.2021.651473. View