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2000
Volume 21, Issue 6
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Background

The role of Forkhead Box D2 (FOXD2) in head and neck squamous cell carcinoma (HNSC) has never been studied.

Objectives

Our object was to explore the role of FOXD2 in HNSC.

Methods

Clinical data for patients with HNSC was obtained from TCGA. Our study examined the atypical expression of FOXD2 in both HNSC and pan-cancer, along with its diagnostic and prognostic implications, as well as the association between FOXD2 expression and clinical characteristics, immune infiltration, immune checkpoint genes, and MSI. Gene set enrichment analysis (GESA) was used to investigate the potential regulation network of FOXD2 in HNSC. We analyze the genomic alterations of FOXD2 in HNSC. GSE13397 and qRT-PCR were used for the validation of FOXD2 expression.

Results

FOXD2 was aberrantly expressed in 24 tumors. FOXD2 was significantly up-regulated in HNSC compared to normal head and neck tissue ( < 0.001). High FOXD2 expression was associated with the histologic grade of the patient with HNSC ( < 0.001), lymphovascular infiltration ( = 0.002) and lymph node neck dissection ( = 0.002). In HNSC, an autonomous correlation between FOXD2 expression and OS was observed (HR: 1.36; 95% CI: 1.04-1.78; = 0.026). FOXD2 was associated with the neuronal system, neuroactive ligand-receptor interaction, and retinoblastoma gene in cancer. FOXD2 was associated with immune infiltration, immune checkpoints, and MSI. The somatic mutation rate of FOXD2 in HNSC was 0.2%. FOXD2 was significantly up-regulated in HNSC cell lines.

Conclusion

Our findings suggest that FOXD2 has the potential to serve as a prognostic biomarker and immunotherapeutic target for individuals with HNSC.

© 2025 Bentham Science Publishers
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2024-04-16
2025-12-05

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References

  1. MillerK.D. NogueiraL. DevasiaT. MariottoA.B. YabroffK.R. JemalA. KramerJ. SiegelR.L. Cancer treatment and survivorship statistics, 2022.CA Cancer J. Clin.202272540943610.3322/caac.21731 35736631
     [Google Scholar]
  2. CohenE.E.W. LaMonteS.J. ErbN.L. BeckmanK.L. SadeghiN. HutchesonK.A. StubblefieldM.D. AbbottD.M. FisherP.S. SteinK.D. LymanG.H. ChapmanP.M.L. American cancer society head and neck cancer survivorship care guideline.CA Cancer J. Clin.201666320323910.3322/caac.21343 27002678
     [Google Scholar]
  3. BhatG.R. HyoleR.G. LiJ. Head and neck cancer: Current challenges and future perspectives.Adv. Cancer Res.20211526710210.1016/bs.acr.2021.05.002 34353444
     [Google Scholar]
  4. MoghaddamR.M. AbbaszadehH. Gene polymorphisms and prognosis of head and neck squamous cell carcinoma: A systematic review.Rep. Pract. Oncol. Radiother.20222761045105710.5603/RPOR.a2022.0109 36632296
     [Google Scholar]
  5. EconomopoulouP. AgelakiS. PerisanidisC. GiotakisE.I. PsyrriA. The promise of immunotherapy in head and neck squamous cell carcinoma.Ann. Oncol.20162791675168510.1093/annonc/mdw226 27380958
     [Google Scholar]
  6. SimF. LeidnerR. BellR.B. Immunotherapy for head and neck cancer.Oral Maxillofac. Surg. Clin. North Am.20193118510010.1016/j.coms.2018.09.002 30449528
     [Google Scholar]
  7. KatohM. KatohM. Human FOX gene family (Review).Int. J. Oncol.200425514951500 15492844
     [Google Scholar]
  8. PohlB.S. KnöchelW. Temporal and spatial expression patterns of FoxD2 during the early development of Xenopus laevis.Mech. Dev.20021111-218118410.1016/S0925‑4773(01)00617‑7 11804794
     [Google Scholar]
  9. ErnstssonS. BetzR. LagercrantzS. LarssonC. ErickssonS. CederbergA. CarlssonP. EnerbäckS. Cloning and characterization of freac-9 (FKHL17), a novel kidney-expressed human forkhead gene that maps to chromosome 1p32-p34.Genomics1997461788510.1006/geno.1997.4986 9403061
     [Google Scholar]
  10. JohanssonC.C. DahleM.K. BlomqvistS.R. GrønningL.M. AandahlE.M. EnerbäckS. TaskénK. A winged helix forkhead (FOXD2) tunes sensitivity to cAMP in T lymphocytes through regulation of cAMP-dependent protein kinase RIalpha.J. Biol. Chem.200327819175731757910.1074/jbc.M300311200 12621056
     [Google Scholar]
  11. KimH.M. KangB. ParkS. ParkH. KimC.J. LeeH. YooM. KweonM.N. Im, S.H.; Kim, T.I.; Roh, T.Y. Forkhead box protein D2 suppresses colorectal cancer by reprogramming enhancer interactions.Nucleic Acids Res.202351126143615510.1093/nar/gkad361 37158258
     [Google Scholar]
  12. WeinsteinJ.N. CollissonE.A. MillsG.B. ShawK.R.M. OzenbergerB.A. EllrottK. ShmulevichI. SanderC. StuartJ.M. The cancer genome atlas pan-cancer analysis project.Nat. Genet.201345101113112010.1038/ng.2764 24071849
     [Google Scholar]
  13. ColapricoA. SilvaT.C. OlsenC. GarofanoL. CavaC. GaroliniD. SabedotT.S. MaltaT.M. PagnottaS.M. CastiglioniI. CeccarelliM. BontempiG. NoushmehrH. TCGAbiolinks: An R/bioconductor package for integrative analysis of TCGA data.Nucleic Acids Res.2016448e7110.1093/nar/gkv1507 26704973
     [Google Scholar]
  14. HanQ. CuiZ. WangQ. PangF. LiD. WangD. Upregulation of OTX2-AS1 is associated with immune infiltration and predicts prognosis of gastric cancer.Technol. Cancer Res. Treat.2023221533033823115409110.1177/15330338231154091 36740995
     [Google Scholar]
  15. ZhaoY. ZhaoJ. ZhongM. ZhangQ. YanF. FengY. GuoY. The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma.Front. Genet.20221398224110.3389/fgene.2022.982241 36204311
     [Google Scholar]
  16. ChenY.C. LiD.B. WangD.L. PengH. Comprehensive analysis of distal-less homeobox family gene expression in colon cancer.World J. Gastrointest. Oncol.20231561019103510.4251/wjgo.v15.i6.1019 37389108
     [Google Scholar]
  17. LinZ. HuangW. YiY. LiD. XieZ. LiZ. YeM. LncRNA ADAMTS9-AS2 is a prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma.Int. J. Gen. Med.2021148541855510.2147/IJGM.S340683 34849000
     [Google Scholar]
  18. RenL. PanX. NingL. GongD. HuangJ. DengK. XieL. ZhangY. Construction of a combined hypoxia-related genes model for hepatocellular carcinoma prognosis.Curr. Computeraided Drug Des.202319215016110.2174/1573409919666221223123610 36567292
     [Google Scholar]
  19. SubramanianA. TamayoP. MoothaV.K. MukherjeeS. EbertB.L. GilletteM.A. PaulovichA. PomeroyS.L. GolubT.R. LanderE.S. MesirovJ.P. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles.Proc. Natl. Acad. Sci. USA200510243155451555010.1073/pnas.0506580102 16199517
     [Google Scholar]
  20. YiW. ShenH. SunD. XuY. FengY. LiD. WangC. Low expression of long noncoding RNA SLC26A4 antisense RNA 1 is an independent prognostic biomarker and correlate of immune infiltrates in breast cancer.Med. Sci. Monit.202127e934522 34880202
     [Google Scholar]
  21. ChenJ. TangH. LiT. JiangK. ZhongH. WuY. HeJ. LiD. LiM. CaiX. Comprehensive analysis of the expression, prognosis, and biological significance of OVOLs in breast cancer.Int. J. Gen. Med.2021143951396010.2147/IJGM.S326402 34345183
     [Google Scholar]
  22. HänzelmannS. CasteloR. GuinneyJ. GSVA: gene set variation analysis for microarray and RNA-Seq data.BMC Bioinformatics2013141710.1186/1471‑2105‑14‑7 23323831
     [Google Scholar]
  23. BindeaG. MlecnikB. TosoliniM. KirilovskyA. WaldnerM. ObenaufA.C. AngellH. FredriksenT. LafontaineL. BergerA. BrunevalP. FridmanW.H. BeckerC. PagèsF. SpeicherM.R. TrajanoskiZ. GalonJ. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.Immunity201339478279510.1016/j.immuni.2013.10.003 24138885
     [Google Scholar]
  24. YangD. LiuM. JiangJ. LuoY. WangY. ChenH. LiD. WangD. YangZ. ChenH. Comprehensive analysis of DMRT3 as a potential biomarker associated with the immune infiltration in a pan-cancer analysis and validation in lung adenocarcinoma.Cancers20221424622010.3390/cancers14246220 36551704
     [Google Scholar]
  25. LinJ.C. WangC.C. JiangR.S. WangW.Y. LiuS.A. Microsatellite alteration in head and neck squamous cell carcinoma patients from a betel quid-prevalent region.Sci. Rep.2016612261410.1038/srep22614 27009367
     [Google Scholar]
  26. ZhangG. LiT. TanG. SongY. LiuQ. WangK. AiJ. ZhouZ. LiW. Identity ofMMP1 and its effects on tumor progression in head and neck squamous cell carcinoma.Cancer Med.202211122516253010.1002/cam4.4623 35426219
     [Google Scholar]
  27. SobocińskaJ. NowakowskaJ. MolendaS. OlechnowiczA. GuglasK. MasłońK.J. KazimierczakU. MachnikM. OleksiewiczU. TeresiakA. LamperskaK. KolendaT. Zinc finger proteins in head and neck squamous cell carcinomas: ZNF540 may serve as a biomarker.Curr. Oncol.202229129896991510.3390/curroncol29120779 36547193
     [Google Scholar]
  28. YeS. WangD. JinM. DuJ. ChenX. ZhangH. ZhouC. FangS. LiuK. High eukaryotic initiation factor 5A2 expression predicts poor prognosis and may participate in the SNHG16/MIR ‐10b‐5p/EIF5A2 regulatory axis in head and neck squamous cell carcinoma.J. Clin. Lab. Anal.2023371e2482010.1002/jcla.24820 36550070
     [Google Scholar]
  29. ZhangH. LiZ. ZhengY. Identifying the therapeutic and prognostic role of the CD8+ T cell-related gene ALDH2 in head and neck squamous cell carcinoma.Cancer Inform.20222110.1177/11769351221139252 36570380
     [Google Scholar]
  30. LiuH. LiY. Potential roles of cornichon family AMPA receptor auxiliary protein 4 (CNIH4) in head and neck squamous cell carcinoma.Cancer Biomark.202235443945010.3233/CBM‑220143 36404537
     [Google Scholar]
  31. PanX. XueL. SunY. Spermine synthase (SMS) serves as a prognostic biomarker in head and neck squamous cell carcinoma: a bioinformatics analysis.Ann. Transl. Med.20221022121310.21037/atm‑22‑5014 36544695
     [Google Scholar]
  32. FeiT. ZhouE.C. WangX.J. FOXD2 regulations IQGAP3 mediated Ca 2+ signaling pathway to facilitate gastric adenocarcinoma cell promotion.Kaohsiung J. Med. Sci.202339111087109510.1002/kjm2.12756 37724892
     [Google Scholar]
  33. Van Der NieuwenhuijsenH.L. DitsN.F. JensterG. Gene expression of forkhead transcription factors in the normal and diseased human prostate.BJU Int.2009103111574158010.1111/j.1464‑410X.2009.08351.x 19220249
     [Google Scholar]
  34. RiedhammerK. M. NguyenT. T. KoşukcuC. WackC. J. LiY. BatzirN. A. Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).Kidney Int. 2023.202338154558
     [Google Scholar]
  35. ZhengH. HuaJ. LiH. HeW. ChenX. JiY. LiQ. Comprehensive analysis of the expression of N6-methyladenosine RNA methylation regulators in pulmonary artery hypertension.Front. Genet.20221397474010.3389/fgene.2022.974740 36171892
     [Google Scholar]
  36. OkabeM. MotojimaM. MiyazakiY. PastanI. YokooT. MatsusakaT. Global polysome analysis of normal and injured podocytes.Am. J. Physiol. Renal Physiol.20193162F241F25210.1152/ajprenal.00115.2018 30379099
     [Google Scholar]
  37. JonssonH. PengS.L. Forkhead transcription factors in immunology.Cell. Mol. Life Sci.200562439740910.1007/s00018‑004‑4365‑8 15719167
     [Google Scholar]
  38. ChalmersZ.R. ConnellyC.F. FabrizioD. GayL. AliS.M. EnnisR. SchrockA. CampbellB. ShlienA. ChmieleckiJ. HuangF. HeY. SunJ. TaboriU. KennedyM. LieberD.S. RoelsS. WhiteJ. OttoG.A. RossJ.S. GarrawayL. MillerV.A. StephensP.J. FramptonG.M. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden.Genome Med.2017913410.1186/s13073‑017‑0424‑2 28420421
     [Google Scholar]
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Comprehensive Analysis and Experimental Validation of FOXD2 as a Novel Potential Prognostic Biomarker Associated with Immune Infiltration in Head and Neck Squamous Cell Carcinoma
Curr. Computeraided Drug Des. 21, 860 (2025); https://doi.org/10.2174/0115734099302492240405065505
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  • Article Type:     Research Article
Keyword(s): FOXD2; Head and neck squamous cell carcinoma; immune infiltration; MSI; prognosis; therapeutic target

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