Skip to main content

Advertisement

SpringerLink
Log in

Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Background/aims

Tripartite motif-containing 3 (TRIM3) is a member of the TRIM protein family which is known to be involved in development of numerous tumor types. However, the prognostic role of TRIM3 in gastric cancer (GC) remained to be clarified. The aim of this study was to evaluate the expression pattern and prognostic significance of TRIM3 gene and its relationship with β-catenin, CyclinD, and BCL2 expression in patients with GC.

Methods

A total of 40 fresh primary gastric cancer tumors and their matched adjacent noncancerous tissues were selected from the First Affiliated Hospital of Mashhad University. Real-time quantitative RT-PCR was performed to evaluate differences in TRIM3 expression in GC and normal tissues. The correlation between TRIM3 expression level and patients’ overall survival, some clinicopathological variables, and β-catenin, CyclinD, and BCL-2 genes expression level were also studied. Moreover, patients were divided in two groups according to the TRIM3 expression levels: low and high.

Results

Compared to noncancerous tissues, TRIM3 expression in GC tissues was significantly increased (fold change = 1.58). Kaplan–Meier survival analysis revealed a significant difference of patient survival according to TRIM3 expression status (P = 0.012). Low TRIM3 expression was associated with shorter overall survival and was an independent predictor for poor prognosis in GC patients (HR, 1.25; 95%CI, 1.02-1.60; P = 0.045). Expression of TRIM3 was negatively correlated with expression of β-catenin, BCL-2, and CyclinD as genes for proliferation, apoptosis, and the cell cycle in GC patients.

Conclusions

This study demonstrates that decreased level of TRIM3 mRNA expression is associated with poor prognosis in patients with gastric cancer. TRIM3 may play a protective role in gastric cancer by relieving the effects of cancer progressive genes and could be considered for further investigations as a prognostic biomarker.

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

Similar content being viewed by others

References

  1. Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018;10:239–48.

    Article  CAS  Google Scholar 

  2. Malekzadeh R, Derakhshan MH, Malekzadeh Z. Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med. 2009;12(6):576–83.

    PubMed  Google Scholar 

  3. Yusefi AR, Lankarani KB, Bastani P, Radinmanesh M, Kavosi Z. Risk factors for gastric cancer: a systematic review. Asian Pac J Cancer Prev. 2018;19:591.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Poorolajal J, Moradi L, Mohammadi Y, Cheraghi Z, Gohari-Ensaf F. Risk factors for stomach cancer: a systematic review and meta-analysis. Epidemiol Health. 2020;42:e2020004.

    Article  Google Scholar 

  5. Ye DM, Xu G, Ma W, Li Y, Luo W, Xiao Y, et al. Significant function and research progress of biomarkers in gastric cancer. Oncol Lett. 2020;19:17–29.

  6. Zhou C, Zhong X, Song Y, Shi J, Wu Z, Guo Z, et al. Prognostic biomarkers for gastric cancer: an umbrella review of the evidence. Front Oncol. 2019;9:1321.

  7. Mohammadi M, Moradi A, Farhadi J, Akbari A, Pourmandi S, Mehrad-Majd H. Prognostic value of visfatin in various human malignancies: a systematic review and meta-analysis. Cytokine. 2020;127:154964.

    Article  CAS  Google Scholar 

  8. Arjmand MH, Moradi A, Akbari A, Mehrad-Majd H. Clinical significance of circulating omentin levels in various malignant tumors: evidence from a systematic review and meta-analysis. Cytokine. 2020;125:154869.

    Article  CAS  Google Scholar 

  9. Mehrad-Majd H, Ravanshad S, Moradi A, Khansalar N, Sheikhi M, Akhtari J. Decreased expression of lncRNA loc285194 as an independent prognostic marker in cancer: a systematic review and meta-analysis. Pathol Res Pract. 2019;215:152426.

    Article  CAS  Google Scholar 

  10. Mohammadi M, Mianabadi F, Mehrad-Majd H. Circulating visfatin levels and cancers risk: A systematic review and meta-analysis. J Cell Physiol. 2019;234:5011–22.

    Article  CAS  Google Scholar 

  11. Mehrad-Majd H, Akhtari J, Haerian MS, Ravanshad Y. Clinicopathological and prognostic value of lncRNA PANDAR expression in solid tumors: evidence from a systematic review and meta-analysis. J Cell Physiol. 2019;234:4206–16.

    Article  CAS  Google Scholar 

  12. Kim J, Kim Y, Lee K-A. Ethnic differences in gastric cancer genetic susceptibility: Allele flips of interleukin gene. World J Gastroenterol: WJG. 2014;20:4558–65.

    Article  CAS  Google Scholar 

  13. Meroni G. Genomics and evolution of the TRIM gene family. In: TRIM/RBCC Proteins. New York: Springer; 2012. p. 1–9. 

  14. Gatt ME, Takada K, Mani M, Lerner M, Pick M, Hideshima T, et al. TRIM 13 (RFP 2) downregulation decreases tumour cell growth in multiple myeloma through inhibition of NF K appa B pathway and proteasome activity. Br J Haematol. 2013;162:210–20.

  15. Boulay J-L, Stiefel U, Taylor E, Dolder B, Merlo A, Hirth F. Loss of heterozygosity of TRIM3 in malignant gliomas. BMC Cancer. 2009;9:71.

    Article  Google Scholar 

  16. Liu Y, Raheja R, Yeh N, Ciznadija D, Pedraza AM, Ozawa T, et al. TRIM3, a tumor suppressor linked to regulation of p21 Waf1/Cip1. Oncogene. 2014;33:308–15.

  17. Piao M-Y, Cao H-L, He N-N, Xu M-Q, Dong W-X, Wang W-Q, et al. Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development. Scand J Gastroenterol. 2016;51:572–82.

  18. Wang X, Zhang Y, Pei X, Guo G, Xue B, Duan X, Dou D. TRIM3 inhibits P53 signaling in breast cancer cells. Cancer Cell Int. 2020;20:559. https://doi.org/10.1186/s12935-020-01630-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Li Y, Zhu H, Wang J, Qian X, Li N. miR-4513 promotes breast cancer progression through targeting TRIM3. Am J Transl Res. 2019;11:2431.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Chao J, Zhang X-F, Pan Q-Z, Zhao J-J, Jiang S-S, Wang Y, et al. Decreased expression of TRIM3 is associated with poor prognosis in patients with primary hepatocellular carcinoma. Med Oncol. 2014;31:102.

  21. Fu H, Yang H, Zhang X, Wang B, Mao J, Li X, et al. Exosomal TRIM3 is a novel marker and therapy target for gastric cancer. J Exp Clin Cancer Res. 2018;37:162.

  22. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  Google Scholar 

  23. Huo X, Li S, Shi T, Suo A, Ruan Z, Yao Y. Tripartite motif 16 inhibits epithelial–mesenchymal transition and metastasis by down-regulating sonic hedgehog pathway in non-small cell lung cancer cells. Biochem Biophys Res Commun. 2015;460:1021–8.

    Article  CAS  Google Scholar 

  24. Qi L, Lu Z, Sun Y-H, Song H-T, Xu W-K. TRIM16 suppresses the progression of prostate tumors by inhibiting the snail signaling pathway. Int J Mol Med. 2016;38:1734–42.

    Article  CAS  Google Scholar 

  25. Chiurillo MA. Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review. World J Exp Med. 2015;5:84–102.

    Article  Google Scholar 

  26. Zhou Z-Y, Yang G-Y, Zhou J, Yu M-H. Significance of TRIM29 and β-catenin expression in non-small-cell lung cancer. J Chin Med Assoc. 2012;75:269–74.

    Article  CAS  Google Scholar 

  27. Zhou Z, Liu Y, Ma M, Chang L. Knockdown of TRIM44 inhibits the proliferation and invasion in papillary thyroid cancer cells through suppressing the Wnt/β-catenin signaling pathway. Biomed Pharmacother. 2017;96:98–103.

    Article  CAS  Google Scholar 

  28. Takano Y, Kato Y, Masuda M, Ohshima Y, Okayasu I. Cyclin D2, but not cyclin D1, overexpression closely correlates with gastric cancer progression and prognosis. J Pathol. 1999;189:194–200.

    Article  CAS  Google Scholar 

  29. Yu J, Leung W, Ng E, To K, Ebert M, Go M, et al. Effect of Helicobacter pylori eradication on expression of cyclin D2 and p27 in gastric intestinal metaplasia. Aliment Pharmacol Ther. 2001;15:1505–11.

  30. Shan YS, Hsu HP, Lai MD, Hung YH, Wang CY, Yen MC, et al. Cyclin D1 overexpression correlates with poor tumor differentiation and prognosis in gastric cancer. Oncol Lett. 2017;14:4517–26.

  31. Gryko M, Pryczynicz A, Zareba K, Kędra B, Kemona A, Guzińska-Ustymowicz K. The expression of Bcl-2 and BID in gastric cancer cells. J Immunol Res. 2014;2014:953203. https://doi.org/10.1155/2014/953203.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tsamandas AC, Kardamakis D, Tsiamalos P, Liava A, Tzelepi V, Vassiliou V, et al. The potential role of Bcl-2 expression, apoptosis and cell proliferation (Ki-67 expression) in cases of gastric carcinoma and correlation with classic prognostic factors and patient outcome. Anticancer Res. 2009;29:703–9.

  33. Saegusa M, Takano Y, Kamata Y, Okayasu I. Bcl-2 expression and allelic loss of thep53 gene in gastric carcinomas. J Cancer Res Clin Oncol. 1996;122:427–32.

    Article  CAS  Google Scholar 

  34. Yildirim M, Suren D, Goktas S, Dilli U, Kaya C, Copuroglu R, et al. The predictive role of Bcl-2 expression in operable locally advanced or metastatic gastric carcinoma. J BUON. 2012;17:106–9.

  35. Smith L, Berrieman HK, O’Kane SL, Campbell A, Maraveyas A, Cawkwell L. Immunohistochemical detection of apoptotic markers in gastric cancer. Oncol Res. 2006;15:441–4.

  36. Van der Woude C, Kleibeuker J, Tiebosch A, Homan M, Beuving A, Jansen P, et al. Diffuse and intestinal type gastric carcinomas differ in their expression of apoptosis related proteins. J Clin Pathol. 2003;56:699–702.

Download references

Acknowledgments

We would like to thank all the study participants for their cooperation. This work was supported by Research Project No. 951677 as a PhD thesis, financed by Mashhad University of Medical Sciences. We would also like to thank the Clinical Research Development Center, Ghaem Hospital, Mashhad University of Medical Sciences, for their assistance in this manuscript.

Author information

Author notes

  1. Javad Farhadi and Ladan Goshayeshi contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran

    Javad Farhadi & Jamshid Mehrzad

  2. Department of Gastroenterology and Hepatology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Ladan Goshayeshi

  3. Department of Chemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran

    Alireza Motavalizadehkakhky

  4. Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Hassan Mehrad-Majd

  5. Clinical Research Development Unit, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, P.O. Box: 9176699199, Mashhad, Iran

    Hassan Mehrad-Majd

Authors
  1. Javad Farhadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ladan Goshayeshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alireza Motavalizadehkakhky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jamshid Mehrzad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hassan Mehrad-Majd
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study concept and design: Mehrad-Majd H, Mehrzad J.

Acquisition of data: Farhdi J, Goshayeshi L.

Statistical analysis: Mehrad-Majd H, Farhadi J.

Drafting of the manuscript: Mehrad-Majd H, Farhdi J, Motavalizadehkakhky A.

Study supervision: Mehrad-Majd H.

Corresponding authors

Correspondence to Jamshid Mehrzad or Hassan Mehrad-Majd.

Ethics declarations

Conflict of interest

The authors declare that they have conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Farhadi, J., Goshayeshi, L., Motavalizadehkakhky, A. et al. Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer. J Gastrointest Canc 53, 179–186 (2022). https://doi.org/10.1007/s12029-020-00563-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-020-00563-0

Keywords

Search

Navigation