FHOD1 is a promising biomarker for diagnosis, prognosis, and immunotherapy in colorectal cancer

  • Yanan Li Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
  • Hua Zuo Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Department of General Surgery, Renhe Hospital, Shanghai 200431, China
  • Zhihong Liu Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
  • Ziyu Wu Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
  • Zeyang Zhou Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
  • Jianbo Deng Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
  • Xiaodong Yang Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
DOI: https://doi.org/10.62617/mcb1257
Keywords: FHOD1; colorectal cancer; prognosis; immune infiltration; tumor microenvironment; drug sensitivity; cell proliferation; migration
Article ID: 1257

Abstract

FHOD1 is a crucial regulator of cellular actin dynamics, and growing evidence suggests its involvement in tumorigenesis. Nevertheless, the precise function of FHOD1 in colorectal cancer (CRC) is still not well-defined. FHOD1 expression was analyzed using TIMER 2.0, and its prognostic value was assessed using the Kaplan-Meier Plotter. Functional analysis was performed via LinkedOmics, and its role in immune infiltration was investigated using the TISCH2 database and GSVA package. Drug sensitivity related to FHOD1 was evaluated with R software. Additionally, the CCK-8 assay, colony formation assay, wound-healing assay, and Transwell migration assay were used to evaluate the impact of FHOD1 on the proliferation and migration of colorectal cancer cells. Our study proved that FHOD1 expression was substantially higher in CRC tissues than in normal tissues, correlating with poorer patient prognosis. Functional analysis indicated that FHOD1 was involved in immune-related processes and the tumor microenvironment, particularly affecting numerous types of immune cells, such as natural killer cells and T cells. FHOD1 expression was positively associated with sensitivity to multiple chemotherapeutic agents. Finally, knockdown of FHOD1 in HCT116 and RKO NL cell lines impaired cell proliferation and migration, highlighting its potential as a target for treatment in managing CRC. In conclusion, these findings underscore the importance of FHOD1 in CRC progression and treatment strategies.

References

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2024; 74(3): 229-263. doi: 10.3322/caac.21834

2. Shi X, Zhao S, Cai J, et al. Active FHOD1 promotes the formation of functional actin stress fibers. Biochemical Journal. 2019; 476(20): 2953-2963. doi: 10.1042/bcj20190535

3. Antoku S, Schwartz TU, Gundersen GG. FHODs: Nuclear tethered formins for nuclear mechanotransduction. Frontiers in Cell and Developmental Biology. 2023; 11. doi: 10.3389/fcell.2023.1160219

4. Jurmeister S, Baumann M, Balwierz A, et al. MicroRNA-200c Represses Migration and Invasion of Breast Cancer Cells by Targeting Actin-Regulatory Proteins FHOD1 and PPM1F. Molecular and Cellular Biology. 2012; 32(3): 633-651. doi: 10.1128/mcb.06212-11

5. Heuser VD, Mansuri N, Mogg J, et al. Formin Proteins FHOD1 and INF2 in Triple-Negative Breast Cancer: Association With Basal Markers and Functional Activities. Breast Cancer: Basic and Clinical Research. 2018; 12. doi: 10.1177/1178223418792247

6. Peippo M, Gardberg M, Kronqvist P, et al. Characterization of Expression and Function of the Formins FHOD1, INF2, and DAAM1 in HER2-Positive Breast Cancer. Journal of Breast Cancer. 2023; 26(6): 525. doi: 10.4048/jbc.2023.26.e47

7. Gardberg M, Kaipio K, Lehtinen L, et al. FHOD1, a Formin Upregulated in Epithelial-Mesenchymal Transition, Participates in Cancer Cell Migration and Invasion. PLoS ONE. 2013; 8(9): e74923. doi: 10.1371/journal.pone.0074923

8. Peippo M, Gardberg M, Lamminen T, et al. FHOD1 formin is upregulated in melanomas and modifies proliferation and tumor growth. Experimental Cell Research. 2017; 350(1): 267-278. doi: 10.1016/j.yexcr.2016.12.004

9. Heuser VD, Kiviniemi A, Lehtinen L, et al. Multiple formin proteins participate in glioblastoma migration. BMC Cancer. 2020; 20(1). doi: 10.1186/s12885-020-07211-7

10. Mansuri N, Heuser VD, Birkman EM, et al. FHOD1 and FMNL1 formin proteins in intestinal gastric cancer: correlation with tumor-infiltrating T lymphocytes and molecular subtypes. Gastric Cancer. 2021; 24(6): 1254-1263. doi: 10.1007/s10120-021-01203-7

11. Jiang C, Yuan B, Hang B, et al. FHOD1 is upregulated in gastric cancer and promotes the proliferation and invasion of gastric cancer cells. Oncology Letters. 2021; 22(4). doi: 10.3892/ol.2021.12973

12. Hui L, Chen Y. Tumor microenvironment: Sanctuary of the devil. Cancer Letters. 2015; 368(1): 7-13. doi: 10.1016/j.canlet.2015.07.039

13. Kim J, Bae JS. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment. Mediators of Inflammation. 2016; 2016: 1-11. doi: 10.1155/2016/6058147

14. Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacology & Therapeutics. 2021; 221: 107753. doi: 10.1016/j.pharmthera.2020.107753

15. Ganini C, Amelio I, Bertolo R, et al. Global mapping of cancers: The Cancer Genome Atlas and beyond. Molecular Oncology. 2021; 15(11): 2823-2840. doi: 10.1002/1878-0261.13056

16. Nassar LR, Barber GP, Benet-Pagès A, et al. The UCSC Genome Browser database: 2023 update. Nucleic Acids Research. 2022; 51(D1): D1188-D1195. doi: 10.1093/nar/gkac1072

17. Li T, Fu J, Zeng Z, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Research. 2020; 48(W1): W509-W514. doi: 10.1093/nar/gkaa407

18. Vasaikar SV, Straub P, Wang J, et al. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Research. 2017; 46(D1): D956-D963. doi: 10.1093/nar/gkx1090

19. Kanehisa M, Furumichi M, Sato Y, et al. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Research. 2022; 51(D1): D587-D592. doi: 10.1093/nar/gkac963

20. Gene Ontology Consortium. The Gene Ontology resource: enriching a GOld mine. Nucleic Acids Res; 2021.

21. Han Y, Wang Y, Dong X, et al. TISCH2: expanded datasets and new tools for single-cell transcriptome analyses of the tumor microenvironment. Nucleic Acids Research. 2022; 51(D1): D1425-D1431. doi: 10.1093/nar/gkac959

22. Luna A, Elloumi F, Varma S, et al. CellMiner Cross-Database (CellMinerCDB) version 1.2: Exploration of patient-derived cancer cell line pharmacogenomics. Nucleic Acids Research. 2020; 49(D1): D1083-D1093. doi: 10.1093/nar/gkaa968

23. Shin AE, Giancotti FG, Rustgi AK. Metastatic colorectal cancer: mechanisms and emerging therapeutics. Trends in Pharmacological Sciences. 2023; 44(4): 222-236. doi: 10.1016/j.tips.2023.01.003

24. Shen T, Liu JL, Wang CY, et al. Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer. Signal Transduction and Targeted Therapy. 2021; 6(1). doi: 10.1038/s41392-021-00501-x

25. Grizzi F. Prognostic value of innate and adaptive immunity in colorectal cancer. World Journal of Gastroenterology. 2013; 19(2): 174. doi: 10.3748/wjg.v19.i2.174

26. Boissière-Michot F, Lazennec G, Frugier H, et al. Characterization of an adaptive immune response in microsatellite-instable colorectal cancer. OncoImmunology. 2014; 3(6): e29256. doi: 10.4161/onci.29256

27. Trimaglio G, Tilkin-Mariamé AF, Feliu V, et al. Colon-specific immune microenvironment regulates cancer progression versus rejection. OncoImmunology. 2020; 9(1). doi: 10.1080/2162402x.2020.1790125

28. Yue JH, Li J, Xu QM. Multi-omics analyses of single cell-derived colorectal cancer organoids reveal intratumor heterogeneity and immune response diversity. bioRxiv; 2022.

29. Peng YP, Zhu Y, Zhang JJ, et al. Comprehensive analysis of the percentage of surface receptors and cytotoxic granules positive natural killer cells in patients with pancreatic cancer, gastric cancer, and colorectal cancer. Journal of Translational Medicine. 2013; 11(1). doi: 10.1186/1479-5876-11-262

30. Tang YP, Xie MZ, Li KZ, et al. Prognostic value of peripheral blood natural killer cells in colorectal cancer. BMC Gastroenterology. 2020; 20(1). doi: 10.1186/s12876-020-1177-8

31. Sconocchia G, Eppenberger S, Spagnoli GC, et al. NK cells and T cells cooperate during the clinical course of colorectal cancer. OncoImmunology. 2014; 3(8): e952197. doi: 10.4161/21624011.2014.952197

32. Sun B, Liu M, Cui M, et al. Granzyme B-expressing treg cells are enriched in colorectal cancer and present the potential to eliminate autologous T conventional cells. Immunology Letters. 2020; 217: 7-14. doi: 10.1016/j.imlet.2019.10.007

Published
2025-02-07
How to Cite
Li, Y., Zuo, H., Liu, Z., Wu, Z., Zhou, Z., Deng, J., & Yang, X. (2025). FHOD1 is a promising biomarker for diagnosis, prognosis, and immunotherapy in colorectal cancer. Molecular & Cellular Biomechanics, 22(2), 1257. https://doi.org/10.62617/mcb1257
Issue
Vol. 22 No. 2 (2025)
Section
Article

Copyright (c) 2025 Author(s)

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright on all articles published in this journal is retained by the author(s), while the author(s) grant the publisher as the original publisher to publish the article.

Articles published in this journal are licensed under a Creative Commons Attribution 4.0 International, which means they can be shared, adapted and distributed provided that the original published version is cited.