Bioinformatics analysis of FOS expression, prognostic value, and biological significance in breast cancer
Main Article Content
Abstract
This study aimed to investigate the expression profile, prognostic relevance, and potential biological significance of FOS in breast cancer using publicly available datasets and bioinformatics tools, including TCGA-BRCA, Kaplan-Meier Plotter, bc-GenExMiner, GeneMANIA, STRING, DAVID, and miRmap. FOS expression was markedly lower at the mRNA level in primary breast cancer tissues compared with normal breast tissues, and its expression varied according to disease stage and breast cancer subtype. Survival analyses showed that higher FOS expression was associated with better clinical outcomes, including relapse-free and distant metastasis-free survival. Network analyses indicated that FOS/c-Fos was closely connected with members of the JUN/FOS family and the AP-1 transcription factor complex. Functional enrichment analyses indicated that FOS/FOS-related genes/proteins were enriched in transcriptional regulation, estrogen-related signaling, MAPK signaling pathways, and stress responses. In addition, hsa-miR-221-3p and hsa-miR-222-3p were predicted to potentially regulate FOS post-transcriptionally. Overall, FOS may represent a potential biomarker candidate in breast cancer. However, the current findings are mainly based on mRNA-level data and retrospective bioinformatics analyses, and therefore require further validation using protein-level data, multivariable clinical models, and experimental studies.
Article Details
Keywords
FOS, breast cancer, gene expression, prognosis, AP-1, bioinformatics
References
2. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70. doi:10.1038/nature11412
3. Angel P, Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991;1072(2-3):129-157. doi:10.1016/0304-419x(91)90011-9
4. Eferl R, Wagner EF. AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer. 2003;3(11):859-868. doi:10.1038/nrc1209
5. Razavirad A, Gao H, Ghiasvand R, Zhao C, Zendehdel K, Dahlman-Wright K. Expression of activator protein-1 (AP-1) family members in breast cancer. BMC Cancer. 2013;13:441. doi:10.1186/1471-2407-13-441
6. Grossman RL, Heath AP, Ferretti V, et al. Toward a Shared Vision for Cancer Genomic Data. New England Journal of Medicine. 2016;375(12):1109-1112. doi:10.1056/NEJMp1607591
7. Györffy B, Lanczky A, Eklund AC, et al. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat. 2010;123(3):725-731. doi:10.1007/s10549-009-0674-9
8. Jézéquel P, Campone M, Gouraud W, et al. bc-GenExMiner: an easy-to-use online platform for gene prognostic analyses in breast cancer. Breast Cancer Res Treat. 2012;131(3):765-775. doi:10.1007/s10549-011-1457-7
9. Jézéquel P, Frénel JS, Campion L, et al. bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses. Database (Oxford). 2013;2013:bas060. doi:10.1093/database/bas060
10. Szklarczyk D, Nastou K, Koutrouli M, et al. The STRING database in 2025: protein networks with directionality of regulation. Nucleic Acids Res. 2025;53(D1):D730-D737. doi:10.1093/nar/gkae1113
11. Warde-Farley D, Donaldson SL, Comes O, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010;38(Web Server issue):W214-W220. doi:10.1093/nar/gkq537
12. Dennis G, Sherman BT, Hosack DA, et al. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003;4(9):R60.
13. Vejnar CE, Zdobnov EM. miRmap: Comprehensive prediction of microRNA target repression strength. Nucleic Acids Research. 2012;40(22):11673-11683. doi:10.1093/nar/gks901
14. Nguyen MT, Quang MT. Integrated Bioinformatics Analysis of hsa-miR-4783-3p Target Genes and Functions in Prostate Cancer. Pharm Sci As. 2024;51(3):233-240. doi:10.29090/psa.2024.03.24.AP0911
15. Lao T, Quang M, Le T. The Role of hsa-miR-21 and Its Target Genes Involved in Nasopharyngeal Carcinoma. Asian Pac J Cancer Prev. 2021;22(12):4075-4083. doi:10.31557/APJCP.2021.22.12.4075
16. Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017;19(8):649-658. doi:10.1016/j.neo.2017.05.002
17. He H, Sinha I, Fan R, et al. c-Jun/AP-1 overexpression reprograms ERα signaling related to tamoxifen response in ERα-positive breast cancer. Oncogene. 2018;37(19):2586-2600. doi:10.1038/s41388-018-0165-8
18. Liu X, Bai F, Wang Y, et al. Loss of function of GATA3 regulates FRA1 and c-FOS to activate EMT and promote mammary tumorigenesis and metastasis. Cell Death Dis. 2023;14(6):370. doi:10.1038/s41419-023-05888-9
19. Sundqvist A, Vasilaki E, Voytyuk O, et al. TGFβ and EGF signaling orchestrates the AP-1- and p63 transcriptional regulation of breast cancer invasiveness. Oncogene. 2020;39(22):4436-4449. doi:10.1038/s41388-020-1299-z
20. Harris MA, Savas P, Virassamy B, et al. Towards targeting the breast cancer immune microenvironment. Nat Rev Cancer. 2024;24(8):554-577. doi:10.1038/s41568-024-00714-6
21. Stinson S, Lackner MR, Adai AT, et al. miR-221/222 targeting of trichorhinophalangeal 1 (TRPS1) promotes epithelial-to-mesenchymal transition in breast cancer. Sci Signal. 2011;4(186):pt5. doi:10.1126/scisignal.2002258
22. Li D, Zhao Q, Xie L, et al. Fluoride impairs mitochondrial translation by targeting miR-221-3p/c-Fos/RMND1 axis contributing to neurodevelopment defects. Sci Total Environ. 2023;869:161738. doi:10.1016/j.scitotenv.2023.161738
23. Kuhn DE, Martin MM, Feldman DS, Terry AV, Nuovo GJ, Elton TS. Experimental validation of miRNA targets. Methods. 2008;44(1):47-54. doi:10.1016/j.ymeth.2007.09.005
24. Panwalkar P, Khire A, Shirsat N. Validation of microRNA Target Genes Using Luciferase Reporter assay and Western Blot Analysis. Methods Mol Biol. 2022;2423:27-38. doi:10.1007/978-1-0716-1952-0_3