Skip to main content
SpringerLink
Log in

Identification of Low Expression of GSN as a Key Prognosis Gene in Patients with Gastric Carcinoma

  • HUMAN GENETICS
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

Gelsolin (GSN) is an important actin-binding protein. The current studyidentified the potential role of GSN in Gastric cancer (GC) tumorigenesis and prognosis using bioinformatic analysis. The TCGA, GTEx, and GEO databases were used to gain clinicopathological data on GC patients. Expression of GSN across cancers was evaluated. Kaplan–Meier analyses were conducted to evaluatethe prognostic value of GSN, while the association between GSN expression and clinical characteristics in gastric carcinoma was evaluated using the UALCAN database. The potential diagnostic value of GSN was assessed by the construction of ROC curves. The putative underlying cellular mechanisms were investigated by GO and KEGG pathway enrichment analyses. The GSN mRNA was validated by RT-qPCR. GSN mRNA and protein expression were lower in gastric carcinoma tissue than in noncancerous tissue. GO and KEGG enrichment analyses revealed that GSN plays a key regulatory role in actin binding and capping and thec-erbB/EGFR and PI3K/Akt signaling pathways. GSN has a high diagnostic significance, and low GSN expression is associated with shorter overall survival (OS) in gastric carcinoma. GSN expression was a risk factor for the progression-free interval in patients with gastric carcinoma. We observed that the OS rate of patients with higher GSN expression levels was longer, and GSN had significant predictive value for the clinical outcome of GC. GSN expression is involved in the tumorigenesis of gastric carcinoma progression and may regard as a putative diagnostic and prognostic biomarker for gastric carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.
Fig. 8.

DATA AVAILABILITY

Publicly available datasets were analyzed in this study. This data can be found here:

1. https://portal.gdc.cancer.gov/

2. https://kmplot.com/analysis/

3. http://string-db.org

4. http://ualcan.path.uab.edu/index.html

The publicly available database websites were listed in Supplementary Table 1.

REFERENCES

  1. Thrift, A.P. and El-Serag, H.B., Burden of gastric cancer, Clin. Gastroenterol. Hepatol., 2020, vol. 18, no. 3, pp. 534–542.

    Article  PubMed  Google Scholar 

  2. Arnold, M., Abnet, C.C., Neale, R.E., et al., Global burden of 5 major types of gastrointestinal cancer, Gastroenterology, 2020, vol. 159, no. 1, pp. 335–349.е315.

    Article  PubMed  Google Scholar 

  3. Hamashima, C., The burden of gastric cancer, Ann. Transl. Med., 2020, vol. 8, no. 12, p. 734.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Yin, H.L. and Stossel, T.P., Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein, Nature, 1979, vol. 281, no. 5732, pp. 583–586.

    Article  CAS  PubMed  ADS  Google Scholar 

  5. McGough, A.M., Staiger, C.J., Min, J.K., et al., The gelsolin family of actin regulatory proteins: modular structures, versatile functions, FEBS Lett., 2003, vol. 552, nos. 2–3, pp. 75–81.

    Article  CAS  PubMed  Google Scholar 

  6. Zhuo, J., Tan, E.H., Yan, B., et al., Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade, PLoS One, 2012, vol. 7, no. 8, p. e43594.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  7. Kelley, D.Z., Flam, E.L., Guo, T., et al., Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma, Transl. Res., 2018, vol. 202, pp. 109–119.

    Article  CAS  PubMed  Google Scholar 

  8. Vivian, J., Rao, A.A., Nothaft, F.A., et al., Toil enables reproducible, open source, big biomedical data analyses, Nat. Biotechnol., 2017, vol. 35, no. 4, pp. 314–316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chandrashekar, D.S., Bashel, B., Balasubramanya, S.A.H., et al., UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses, Neoplasia, 2017, vol. 19, no. 8, pp. 649–658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Uhlén, M., Fagerberg, L., Hallström, B.M., et al., Proteomics: tissue-based map of the human proteome, Science, 2015, vol. 347, no. 6220, p. 1260419.

    Article  PubMed  Google Scholar 

  11. Uhlen, M. and Zhang, C., A pathology atlas of the human cancer transcriptome, Science, 2017, vol. 357, no. 6352.

  12. Thul, P.J. and Åkesson, L., A subcellular map of the human proteome, Science, 2017, vol. 356, no. 6340.

  13. Zhang, Q., Xia, T., Qi, C., et al., High expression of S100A2 predicts poor prognosis in patients with endometrial carcinoma, BMC Cancer, 2022, vol. 22, no. 1, p. 77.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Xia, S., Lin, Y., Lin, J., et al., Increased expression of TICRR predicts poor clinical outcomes: a potential therapeutic target for papillary renal cell carcinoma, Front. Genet., 2020, vol. 11, p. 605378.

  15. Yu, G., Wang, L.G., Han, Y., et al., clusterProfiler: an R package for comparing biological themes among gene clusters, Omics, 2012, vol. 16, no. 5, pp. 284–287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Deng, R., Hao, J., Han, W., et al., Gelsolin regulates proliferation, apoptosis, migration and invasion in human oral carcinoma cells, Oncol. Lett., 2015, vol. 9, no. 5, pp. 2129–2134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Guo, Y., Zhang, H., Xing, X., et al., Gelsolin regulates proliferation, apoptosis and invasion in natural killer/T-cell lymphoma cells, Biol. Open, 2018, vol. 7, no. 1.

  18. Bai, R., Chen, N., Liang, T., et al., Novel frontiers of treatment for advanced gastric or gastroesophageal junction cancer (GC/GEJC): will immunotherapy be a future direction?, Front. Oncol., 2020, vol. 10, p. 912.

  19. Kanda, Y., Kakutani, K., Yurube, T., A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system, J. Orthop. Res., 2021, vol. 39, no. 3, pp. 525–535.

    Article  CAS  PubMed  Google Scholar 

  20. Li, S., Li, J., Peng, L., et al., Cost-effectiveness of frontline treatment for advanced renal cell carcinoma in the era of immunotherapies, Front. Pharmacol., 2021, vol. 12, p. 718014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yuan, C., Zhang, E., Huang, L., et al., Oral administration of inactivated porcine epidemic diarrhea virus activate DCs in porcine Peyer’s patches, BMC Vet. Res., 2018, vol. 14, no. 1, p. 239.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yuan, C., Zhang, E., Huang, L., et al., Correction to: Oral administration of inactivated porcine epidemic diarrhea virus activate DCs in porcine Peyer’s patches, BMC Vet. Res., 2018, vol. 14, no. 1, p. 303.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Marino, N., Marshall, J.C., Collins, J.W., et al., Nm23-h1 binds to gelsolin and inactivates its actin-severing capacity to promote tumor cell motility and metastasis, Cancer Res., 2013, vol. 73, no. 19, pp. 5949–5962.

    Article  CAS  PubMed  Google Scholar 

  24. Chen, C.C., Chiou, S.H., Yang, C.L., et al., Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer, Oncotarget, 2017, vol. 8, no. 44, pp. 77152–77167.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kim, J.C., Ha, Y.J., Tak, K.H., et al., Opposite functions of GSN and OAS2 on colorectal cancer metastasis, mediating perineural and lymphovascular invasion, respectively, PLoS One, 2018, vol. 13, no. 8, p. e0202856.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Zhu, X., Cai, L., Meng, Q., et al., Gelsolin inhibits the proliferation and invasion of the 786-0 clear cell renal cell carcinoma cell line in vitro, Mol. Med. Rep., 2015, vol. 12, no. 5, pp. 6887–6894.

    Article  CAS  PubMed  Google Scholar 

  27. Noske, A., Denkert, C., Schober, H., et al., Loss of gelsolin expression in human ovarian carcinomas, Eur. J. Cancer, 2005, vol. 41, no. 3, pp. 461–469.

    Article  CAS  PubMed  Google Scholar 

  28. Silacci, P., Mazzolai, L., Gauci, C., et al., Gelsolin superfamily proteins: key regulators of cellular functions, Cell Mol. Life Sci., 2004, vol. 61, nos. 19–20, pp. 2614–2623.

    Article  CAS  PubMed  Google Scholar 

  29. Ma, X., Sun, W., Shen, J., et al., Gelsolin promotes cell growth and invasion through the upregulation of p-AKT and p-P38 pathway in osteosarcoma, Tumour Biol., 2016, vol. 37, no. 6, pp. 7165–7174.

    Article  CAS  PubMed  Google Scholar 

  30. Fu, C. and Jiang, A., Dendritic cells and CD8 T cell immunity in tumor microenvironment, Front. Immunol., 2018, vol. 9, p. 3059.

  31. Nie, S. and Yuan, Y., The role of gastric mucosal immunity in gastric diseases, J. Immunol. Res., 2020, vol. 2020, p. 7927054.

Download references

Funding

This study was supported by the 2020 Chengde Science and Technology Research and Development Plan Project (202006A042) and the project supported by the Natural Science Foundation of Hebei Province (H2019406073).

Author information

Authors and Affiliations

  1. Department of Pathology, Affiliated Hospital of Chengde Medical College, 067000, Chengde, Hebei, China

    M. Hao, X. Zhang, Z. Li, S. Li & C. Li

Authors
  1. M. Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Li.

Ethics declarations

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

All the data were collected and downloaded from TCGA database. As TCGA database is open to the public under specific guidelines, it is confirmed that all written informed consents were achieved. The patients/participants provided their written informed consent to participate in this study.

CONSENT FOR PUBLICATION

All authors have provided consent for the publication of this final version manuscript.

CONFLICT OF INTEREST

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hao, M., Zhang, X., Li, Z. et al. Identification of Low Expression of GSN as a Key Prognosis Gene in Patients with Gastric Carcinoma. Russ J Genet 60, 220–230 (2024). https://doi.org/10.1134/S1022795424020042

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795424020042

Keywords:

Search

Navigation