Overexpression of TRIM37 is Associated with Unfavorable Outcomes in Gastric Cancer Patients

محورهای موضوعی :

Jalil Afshar ¹ , Jamshid Mehrzad ² , Hassan Mehrad-Majd ³ , Jafar Saeidi ⁴

1 - Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran
2 - Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran
3 - Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4 - Department of Physiology, School of Basic Science, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran

تاریخ دریافت : 1402/07/19 تاریخ پذیرش : 1403/09/14 تاریخ انتشار : 1403/05/30

کلید واژه: gastric cancer, Survival, β-catenin, TRIM37, Prognostic factor,

چکیده مقاله :

TRIM37 expression has been shown to be dysregulated in various types of cancers. This study was aimed to assess the clinical significance and potential utility of TRIM37 expression level as an indicator of prognosis in gastric cancer (GC) patients. The potential correlation between TRIM37 and the levels of β-catenin, Cyclin D and BCL2 was also investigated. qRT-PCR was used to determine the expression levels of TRIM37 in 40 fresh GC and their adjacent noncancerous tissues. Statistical analyses were conducted to evaluate the relationship between TRIM37 expression levels, overall survival (OS), various clinicopathological features, and the expression levels of β-catenin, Cyclin D, and Bcl-2. TRIM37 expression was significantly higher in the cancerous tissue samples compared to noncancerous tissues (Fold change=1.92, P=0.007). Moreover, Kaplan-Meier analysis indicated that high TRIM37 group exhibited shorter OS (P=0.003). TRIM37 overexpression was strongly associated with poor prognosis and predicts unfavorable outcomes in GC patients (HR=1.85, 95%CI: 1.28-2.66, P=0.001). A direct correlation was also observed between TRIM37 and elevated levels of β-catenin, a gene known for its role in cell proliferation among GC patients. TRIM37 overexpression is strongly linked with a poor prognosis in GC patients, highlighting its potential as an independent prognostic factor in GC and providing insight into its possible involvement in cancer development through Wnt/β-catenin signaling pathway. However, additional research is required to validate the potential prognostic value of TRIM37 in gastric cancer.

چکیده انگلیسی:

TRIM37 expression has been shown to be dysregulated in various types of cancers. This study was aimed to assess the clinical significance and potential utility of TRIM37 expression level as an indicator of prognosis in gastric cancer (GC) patients. The potential correlation between TRIM37 and the levels of β-catenin, Cyclin D and BCL2 was also investigated. qRT-PCR was used to determine the expression levels of TRIM37 in 40 fresh GC and their adjacent noncancerous tissues. Statistical analyses were conducted to evaluate the relationship between TRIM37 expression levels, overall survival (OS), various clinicopathological features, and the expression levels of β-catenin, Cyclin D, and Bcl-2. TRIM37 expression was significantly higher in the cancerous tissue samples compared to noncancerous tissues (Fold change=1.92, P=0.007). Moreover, Kaplan-Meier analysis indicated that high TRIM37 group exhibited shorter OS (P=0.003). TRIM37 overexpression was strongly associated with poor prognosis and predicts unfavorable outcomes in GC patients (HR=1.85, 95%CI: 1.28-2.66, P=0.001). A direct correlation was also observed between TRIM37 and elevated levels of β-catenin, a gene known for its role in cell proliferation among GC patients. TRIM37 overexpression is strongly linked with a poor prognosis in GC patients, highlighting its potential as an independent prognostic factor in GC and providing insight into its possible involvement in cancer development through Wnt/β-catenin signaling pathway. However, additional research is required to validate the potential prognostic value of TRIM37 in gastric cancer.

منابع و مأخذ:

1. Sung H., Ferlay J., Siegel R. L., Laversanne M., Soerjomataram I., Jemal A., Bray F., 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians. 71(3), 209-249.


2. Li Y., Feng A., 2022. Recent Estimates and Predictions of 5-Year Survival in Patients with Gastric Cancer: A Model-Based Period Analysis. 29, 10732748221099227.


3. Sitarz R., Skierucha M., Mielko J., Offerhaus G.J.A., Maciejewski R., Polkowski W.P., 2018. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 10, 239-248.


4. Matsuoka T., Yashiro M., 2018. Biomarkers of gastric cancer: Current topics and future perspective. World J Gastroenterol. 24 (26), 2818-2832.


5. Pužar Dominkuš P., Hudler P., 2023. Mutational Signatures in Gastric Cancer and Their Clinical Implications. Cancers (Basel). 15(15), 3788.


6. Wu H.H., Lin W.C., Tsai K.W., 2014. Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers. Expert Reviews in Molecular Medicine. 16, e1.


7. Li P., Chen S., Chen H., Mo X., Li T., Shao Y., Xiao B., Guo J., 2015. Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clinica Chimica Acta. 444, 132-136.


8. Gu Y., Chen T., Li G., Yu X., Lu Y., Wang H., Teng L., 2015. LncRNAs: emerging biomarkers in gastric cancer. Future Oncology. 11(17), 2427-2441.


9. Meroni G., 2012. Genomics and evolution of the TRIM gene family. Adv Exp Med Biol. 770, 1-9.


10. Li Y., Wu H., Wu W., Zhuo W., Liu W., Zhang Y., Cheng M., Chen Y.G., Gao N., Yu H., Wang L., Li W., Yang M., 2014. Structural insights into the TRIM family of ubiquitin E3 ligases. Cell Research. 24(6), 762-765.


11. Hatakeyama S., 2017. TRIM Family Proteins: Roles in Autophagy, Immunity, and Carcinogenesis. Trends Biochem Sci. 42(4), 297-311.


12. Bhatnagar S., Gazin C., Chamberlain L., Ou J., Zhu X., Tushir J.S., Virbasius C.M., Lin L., Zhu L.J., Wajapeyee N., Green M.R., 2014. TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein. Nature. 516(7529), 116-120.


13. Domínguez-Calvo A., Gönczy P., 2021. TRIM37: a critical orchestrator of centrosome function. 20 (23), 2443-2451.


14. Hu C. E., Gan J., 2017. TRIM37 promotes epithelial‑mesenchymal transition in colorectal cancer. Mol Med Rep. 15(3), 1057-1062.


15. Jiang J., Yu C., Chen M., Tian S., Sun C., 2015. Over-expression of TRIM37 promotes cell migration and metastasis in hepatocellular carcinoma by activating Wnt/β-catenin signaling. Biochem Biophys Res Commun. 464(4), 1120-1127.


16. Li Y., Deng L., Zhao X., Li B., Ren D., Yu L., Pan H., Gong Q., Song L., Zhou X., Dai T., 2018. Tripartite motif-containing 37 (TRIM37) promotes the aggressiveness of non-small-cell lung cancer cells by activating the NF-κB pathway. 246(3), 366-378.


17. Chen S., He Z., Zhu C., Liu Y., Li L., Deng L., Wang J., Yu C., Sun C., 2020. TRIM37 Mediates Chemoresistance and Maintenance of Stemness in Pancreatic Cancer Cells via Ubiquitination of PTEN and Activation of the AKT-GSK-3β-β-Catenin Signaling Pathway. Front Oncol. 10, 554787.


18. Miao C., Liang C., Li P., Liu B., Qin C., Yuan H., Liu Y., Zhu J., Cui Y., Xu A., Wang S., Su S., Li J., Shao P., Wang Z., 2021. TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner. J Exp Clin Cancer Res. 40(1), 195.


19. Chen D., You X., Pan Y., Liu Q., Cao G., 2018. TRIM37 promotes cell invasion and metastasis by regulating SIP1-mediated epithelial-mesenchymal transition in gastric cancer. Onco Targets Ther. 11, 8803-8813.


20. Nishibeppu K., Komatsu S., Kiuchi J., Kishimoto T., Takashima Y., Shoda K., Arita T., Kosuga T., Konishi H., Shiozaki A., Kubota T., Okamoto K., Fujiwara H., Tsuda H., Otsuji E., 2021. TRIM37 contributes to malignant outcomes and CDDP resistance in gastric cancer. J Cancer. 12(2), 316-325.


21. Zhou Z.Y., Yang G.Y., Zhou J., Yu M.H., 2012. Significance of TRIM29 and β-catenin expression in non-small-cell lung cancer. J Chin Med Assoc. 75(6), 269-274.


22. Farhadi J., Goshayeshi L., Motavalizadehkakhky A., Mehrzad J., Mehrad-Majd H., 2022. Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer. J Gastrointest Cancer. 53(1), 179-186.


23. Afshar J., Mehrzad J., Mehrad-Majd H., Goshayeshi L., Saeidi J., 2021. Prognostic Significance of Tripartite Motif Containing 16 Expression in Patients with Gastric Cancer. Asian Pac J Cancer Prev. 22(8), 2445-2451.


24. Zhu H., Chen Y., Zhang J., Qian C., Qiu W., Shen H., Shen Z., 2020. Knockdown of TRIM37 Promotes Apoptosis and Suppresses Tumor Growth in Gastric Cancer by Inactivation of the ERK1/2 Pathway. Onco Targets Ther. 13, 5479-5491.


25. Farhadi J., Mehrzad J., Mehrad-Majd H., Motavalizadehkakhky A., 2022. Clinical significance of TRIM29 expression in patients with gastric cancer. Gastroenterol Hepatol Bed Bench. 15(2), 131-138.