ISSN: 2008-2258
Vol 15, No 2 (2022): Spring
Clinical significance of TRIM29 expression in patients with gastric cancer
Gastroenterology and Hepatology from Bed to Bench,
,
https://doi.org/10.22037/ghfbb.vi.2452
Abstract
Background: As validated biomarkers for predicting the clinical outcomes of gastric cancer (GC) have not been fully investigated, the present cross-sectional study has aimed to evaluate the prognostic value of tripartite motif-containing 29 (TRIM29) in GC patients.
Methods: The real-time quantitative PCR method was used to detect TRIM29, β-catenin, Cyclin D, and Bcl-2 expression in 40 gastric cancer tissues and adjacent normal tissues. Association of TRIM29 expression level with some clinicopathological features and patients' overall survival (OS) was assessed using several statistical analyses including, Pearson’s correlation test, Kaplan–Meier method, and Cox regression.
Results: Our results showed that TRIM29 expression level was significantly lower in GC tissues compared with that in the corresponding normal tissue (fold change=0.34, p=0.003). In subgroup analysis based on the TRIM29 expression, patients with low TRIM29 expression level exhibited poorer overall survival (HR = 1.25, 95% CI: 1.06-1.47, p=0.007). Low expression of TRIM29 were also associated with increased level of β-catenin, Cyclin D, and Bcl-2 genes expression.
Conclusion: It was concluded that down-regulated expression of TRIM29 is associated with poor prognosis in patients with gastric cancer. TRIM29 may play a protective role in malignant progression of gastric cancer by relieving the effects of cancer progressive genes and could be considered as an independent prognostic marker.
Keywords:
- Gastric cancer
- TRIM29
- β-catenin
- Cyclin D
- Bcl-2
- Survival
- Prognosis
References
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13. Tabernero J, Hozak RR, Yoshino T, Cohn AL, Obermannova R, Bodoky G, et al. Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study. Annals of oncology : official journal of the European Society for Medical Oncology. 2018;29(3):602-9.
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21. Xu M, Hu J, Zhou B, Zhong Y, Lin N, Xu R. TRIM29 prevents hepatocellular carcinoma progression by inhibiting Wnt/β-catenin signaling pathway. Acta biochimica et biophysica Sinica. 2019;51(1):68-77.
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27. Kataoka Y, Okabe H, Yoshizawa A, Minamiguchi S, Yoshimura K, Haga H, et al. HER2 expression and its clinicopathological features in resectable gastric cancer. Gastric Cancer. 2013;16(1):84-93.
28. Bar-Sela G, Hershkovitz D, Haim N, Kaidar-Person O, Shulman K, Ben-Izhak O. The incidence and prognostic value of HER2 overexpression and cyclin D1 expression in patients with gastric or gastroesophageal junction adenocarcinoma in Israel. Oncology letters. 2013;5(2):559-63.
29. Liu X, Chu K-M. E-cadherin and gastric cancer: cause, consequence, and applications. BioMed research international. 2014;2014.
30. Barker N, Clevers H. Catenins, Wnt signaling and cancer. Bioessays. 2000;22(11):961-5.
31. Anbiaee R, Sheibani KM, Torbati P, Jaam H. Abnormal expression of e-cadherin in gastric adenocarcinoma, and its correlation with tumor histopathology and helicobacter pylori infection. Iranian Red Crescent Medical Journal. 2013;15(3):218.
32. Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, et al. Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. Journal of Clinical Oncology, vol 31 (7) p 868-75. 2013.
33. Graziano F, Arduini F, Ruzzo A, Bearzi I, Humar B, More H, et al. Prognostic analysis of E-cadherin gene promoter hypermethylation in patients with surgically resected, node-positive, diffuse gastric cancer. Clinical Cancer Research. 2004;10(8):2784-9.
34. Liu J, Welm B, Boucher KM, Ebbert MT, Bernard PS. TRIM29 functions as a tumor suppressor in nontumorigenic breast cells and invasive ER+ breast cancer. The American journal of pathology. 2012;180(2):839-47.
35. Ai L, Kim W-J, Alpay M, Tang M, Pardo CE, Hatakeyama S, et al. TRIM29 suppresses TWIST1 and invasive breast cancer behavior. Cancer research. 2014;74(17):4875-87.
36. Fristrup N, Birkenkamp-Demtröder K, Reinert T, Sanchez-Carbayo M, Segersten U, Malmström P-U, et al. Multicenter validation of Cyclin D1, MCM7, TRIM29, and UBE2C as prognostic protein markers in non-muscle–invasive bladder cancer. The American journal of pathology. 2013;182(2):339-49.
37. Xu W, Xu B, Yao Y, Yu X, Cao H, Zhang J, et al. RNA interference against TRIM29 inhibits migration and invasion of colorectal cancer cells. Oncology reports. 2016;36(3):1411-8.
38. Sun H, Dai X, Han B. TRIM29 as a novel biomarker in pancreatic adenocarcinoma. Disease markers. 2014;2014.
39. Xu W, Chen B, Ke D, Chen X. TRIM29 mediates lung squamous cell carcinoma cell metastasis by regulating autophagic degradation of e-cadherin. Aging (Albany NY). 2020;12(13):13488.
40. Hatakeyama S. TRIM family proteins: roles in autophagy, immunity, and carcinogenesis. Trends in biochemical sciences. 2017;42(4):297-311.
41. Liu B, Wen X, Cheng Y. Survival or death: disequilibrating the oncogenic and tumor suppressive autophagy in cancer. Cell death & disease. 2013;4(10):e892-e.
42. Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36(11):1461-73.
43. Nout RA, Bosse T, Creutzberg CL, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, et al. Improved risk assessment of endometrial cancer by combined analysis of MSI, PI3K–AKT, Wnt/β-catenin and P53 pathway activation. Gynecologic oncology. 2012;126(3):466-73.
44. Harmston N, Lim JYS, Arqués O, Palmer HG, Petretto E, Virshup DM, et al. Widespread repression of gene expression in cancer by a Wnt/β-catenin/MAPK pathway. Cancer Research. 2021;81(2):464-75.
45. Du Q, Geller D, editors. Cross-regulation between Wnt and NF-κB signaling pathways. Forum on immunopathological diseases and therapeutics; 2010: Begel House Inc.
46. Zhou Z-Y, Yang G-Y, Zhou J, Yu M-H. Significance of TRIM29 and β-catenin expression in non-small-cell lung cancer. Journal of the Chinese medical association. 2012;75(6):269-74.
47. Qie S, Diehl JA. Cyclin D1, cancer progression, and opportunities in cancer treatment. Journal of Molecular Medicine. 2016;94(12):1313-26.
48. Rieber M, Rieber MS. Cyclin D1 overexpression induces epidermal growth factor-independent resistance to apoptosis linked to BCL-2 in human A431 carcinoma. Apoptosis. 2006;11(1):121-9.
2. Yusefi AR, Lankarani KB, Bastani P, Radinmanesh M, Kavosi Z. Risk factors for gastric cancer: a systematic review. Asian Pacific journal of cancer prevention: APJCP. 2018;19(3):591.
3. Carcas LP. Gastric cancer review. Journal of carcinogenesis. 2014;13.
4. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiology and Prevention Biomarkers. 2014;23(5):700-13.
5. Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, et al. Treatment of gastric cancer. World journal of gastroenterology: WJG. 2014;20(7):1635.
6. Roukos DH, Kappas AM. Perspectives in the treatment of gastric cancer. Nature Clinical Practice Oncology. 2005;2(2):98-107.
7. Lazăr DC, Tăban S, Cornianu M, Faur A, Goldiş A. New advances in targeted gastric cancer treatment. World J Gastroenterol. 2016;22(30):6776-99.
8. Matsuoka T, Yashiro M. Biomarkers of gastric cancer: Current topics and future perspective. World J Gastroenterol. 2018;24(26):2818-32.
9. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Annals of oncology : official journal of the European Society for Medical Oncology. 2008;19(9):1523-9.
10. Betts G, Valentine H, Pritchard S, Swindell R, Williams V, Morgan S, et al. FGFR2, HER2 and cMet in gastric adenocarcinoma: detection, prognostic significance and assessment of downstream pathway activation. Virchows Archiv : an international journal of pathology. 2014;464(2):145-56.
11. Chan AO. E-cadherin in gastric cancer. World J Gastroenterol. 2006;12(2):199-203.
12. Xu DZ, Geng QR, Tian Y, Cai MY, Fang XJ, Zhan YQ, et al. Activated mammalian target of rapamycin is a potential therapeutic target in gastric cancer. BMC cancer. 2010;10:536.
13. Tabernero J, Hozak RR, Yoshino T, Cohn AL, Obermannova R, Bodoky G, et al. Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study. Annals of oncology : official journal of the European Society for Medical Oncology. 2018;29(3):602-9.
14. Li QF, Yao RY, Liu KW, Lv HY, Jiang T, Liang J. Genetic polymorphism of GSTP1: prediction of clinical outcome to oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Journal of Korean medical science. 2010;25(6):846-52.
15. Ozato K, Shin DM, Chang TH, Morse HC, 3rd. TRIM family proteins and their emerging roles in innate immunity. Nature reviews Immunology. 2008;8(11):849-60.
16. Eberhardt W, Haeussler K, Nasrullah U, Pfeilschifter J. Multifaceted Roles of TRIM Proteins in Colorectal Carcinoma. Int J Mol Sci. 2020;21(20):7532.
17. Jaworska AM, Wlodarczyk NA, Mackiewicz A, Czerwinska P. The role of TRIM family proteins in the regulation of cancer stem cell self-renewal. Stem cells (Dayton, Ohio). 2020;38(2):165-73.
18. Zhu X, Wu Y, Miao X, Li C, Yin H, Yang S, et al. High expression of TRIM44 is associated with enhanced cell proliferation, migration, invasion, and resistance to doxorubicin in hepatocellular carcinoma. Tumor Biology. 2016;37(11):14615-28.
19. Marzano F, Caratozzolo MF, Pesole G, Sbisà E, Tullo A. TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance. Biomedicines. 2021;9(3).
20. Dükel M, Streitfeld WS, Tang TC, Backman LR, Ai L, May WS, et al. The Breast Cancer Tumor Suppressor TRIM29 Is Expressed via ATM-dependent Signaling in Response to Hypoxia. The Journal of biological chemistry. 2016;291(41):21541-52.
21. Xu M, Hu J, Zhou B, Zhong Y, Lin N, Xu R. TRIM29 prevents hepatocellular carcinoma progression by inhibiting Wnt/β-catenin signaling pathway. Acta biochimica et biophysica Sinica. 2019;51(1):68-77.
22. Hao L, Wang JM, Liu BQ, Yan J, Li C, Jiang JY, et al. m6A-YTHDF1-mediated TRIM29 upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells. Biochimica et biophysica acta Molecular cell research. 2021;1868(1):118878.
23. Xu R, Hu J, Zhang T, Jiang C, Wang HY. TRIM29 overexpression is associated with poor prognosis and promotes tumor progression by activating Wnt/β-catenin pathway in cervical cancer. Oncotarget. 2016;7(19):28579-91.
24. Durães C, Almeida GM, Seruca R, Oliveira C, Carneiro F. Biomarkers for gastric cancer: prognostic, predictive or targets of therapy? Virchows Archiv. 2014;464(3):367-78.
25. Fisher SB, Fisher KE, Squires III MH, Patel SH, Kooby DA, El‐Rayes BF, et al. HER2 in resected gastric cancer: is there prognostic value? Journal of surgical oncology. 2014;109(2):61-6.
26. Gordon M, Gundacker H, Benedetti J, Macdonald J, Baranda J, Levin W, et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Annals of oncology. 2013;24(7):1754-61.
27. Kataoka Y, Okabe H, Yoshizawa A, Minamiguchi S, Yoshimura K, Haga H, et al. HER2 expression and its clinicopathological features in resectable gastric cancer. Gastric Cancer. 2013;16(1):84-93.
28. Bar-Sela G, Hershkovitz D, Haim N, Kaidar-Person O, Shulman K, Ben-Izhak O. The incidence and prognostic value of HER2 overexpression and cyclin D1 expression in patients with gastric or gastroesophageal junction adenocarcinoma in Israel. Oncology letters. 2013;5(2):559-63.
29. Liu X, Chu K-M. E-cadherin and gastric cancer: cause, consequence, and applications. BioMed research international. 2014;2014.
30. Barker N, Clevers H. Catenins, Wnt signaling and cancer. Bioessays. 2000;22(11):961-5.
31. Anbiaee R, Sheibani KM, Torbati P, Jaam H. Abnormal expression of e-cadherin in gastric adenocarcinoma, and its correlation with tumor histopathology and helicobacter pylori infection. Iranian Red Crescent Medical Journal. 2013;15(3):218.
32. Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, et al. Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. Journal of Clinical Oncology, vol 31 (7) p 868-75. 2013.
33. Graziano F, Arduini F, Ruzzo A, Bearzi I, Humar B, More H, et al. Prognostic analysis of E-cadherin gene promoter hypermethylation in patients with surgically resected, node-positive, diffuse gastric cancer. Clinical Cancer Research. 2004;10(8):2784-9.
34. Liu J, Welm B, Boucher KM, Ebbert MT, Bernard PS. TRIM29 functions as a tumor suppressor in nontumorigenic breast cells and invasive ER+ breast cancer. The American journal of pathology. 2012;180(2):839-47.
35. Ai L, Kim W-J, Alpay M, Tang M, Pardo CE, Hatakeyama S, et al. TRIM29 suppresses TWIST1 and invasive breast cancer behavior. Cancer research. 2014;74(17):4875-87.
36. Fristrup N, Birkenkamp-Demtröder K, Reinert T, Sanchez-Carbayo M, Segersten U, Malmström P-U, et al. Multicenter validation of Cyclin D1, MCM7, TRIM29, and UBE2C as prognostic protein markers in non-muscle–invasive bladder cancer. The American journal of pathology. 2013;182(2):339-49.
37. Xu W, Xu B, Yao Y, Yu X, Cao H, Zhang J, et al. RNA interference against TRIM29 inhibits migration and invasion of colorectal cancer cells. Oncology reports. 2016;36(3):1411-8.
38. Sun H, Dai X, Han B. TRIM29 as a novel biomarker in pancreatic adenocarcinoma. Disease markers. 2014;2014.
39. Xu W, Chen B, Ke D, Chen X. TRIM29 mediates lung squamous cell carcinoma cell metastasis by regulating autophagic degradation of e-cadherin. Aging (Albany NY). 2020;12(13):13488.
40. Hatakeyama S. TRIM family proteins: roles in autophagy, immunity, and carcinogenesis. Trends in biochemical sciences. 2017;42(4):297-311.
41. Liu B, Wen X, Cheng Y. Survival or death: disequilibrating the oncogenic and tumor suppressive autophagy in cancer. Cell death & disease. 2013;4(10):e892-e.
42. Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36(11):1461-73.
43. Nout RA, Bosse T, Creutzberg CL, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, et al. Improved risk assessment of endometrial cancer by combined analysis of MSI, PI3K–AKT, Wnt/β-catenin and P53 pathway activation. Gynecologic oncology. 2012;126(3):466-73.
44. Harmston N, Lim JYS, Arqués O, Palmer HG, Petretto E, Virshup DM, et al. Widespread repression of gene expression in cancer by a Wnt/β-catenin/MAPK pathway. Cancer Research. 2021;81(2):464-75.
45. Du Q, Geller D, editors. Cross-regulation between Wnt and NF-κB signaling pathways. Forum on immunopathological diseases and therapeutics; 2010: Begel House Inc.
46. Zhou Z-Y, Yang G-Y, Zhou J, Yu M-H. Significance of TRIM29 and β-catenin expression in non-small-cell lung cancer. Journal of the Chinese medical association. 2012;75(6):269-74.
47. Qie S, Diehl JA. Cyclin D1, cancer progression, and opportunities in cancer treatment. Journal of Molecular Medicine. 2016;94(12):1313-26.
48. Rieber M, Rieber MS. Cyclin D1 overexpression induces epidermal growth factor-independent resistance to apoptosis linked to BCL-2 in human A431 carcinoma. Apoptosis. 2006;11(1):121-9.
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