Skip to main content
Top
Published in: Medical Oncology 8/2014

01-08-2014 | Original Paper

Decreased expression of TRIM3 is associated with poor prognosis in patients with primary hepatocellular carcinoma

Authors: Jie Chao, Xiao-Fei Zhang, Qiu-Zhong Pan, Jing-Jing Zhao, Shan-Shan Jiang, Ying Wang, Jian-Hua Zhang, Jian-Chuan Xia

Published in: Medical Oncology | Issue 8/2014

Login to get access

Abstract

Tripartite motif-containing 3 (TRIM3) is a member of the tripartite motif (TRIM) protein family and is reported to be involved in the pathogenesis of various cancers. The role of TRIM3 in hepatocellular carcinoma (HCC) is unknown; thus, the goal of this study was to explore the expression level and prognostic value of TRIM3 in HCC. The expression level of TRIM3 in HCC surgically resected tumors and corresponding nontumorous samples was detected by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. The correlation between TRIM3 expression level and the clinicopathological features and prognosis of HCC patients was also analyzed. We observed that TRIM3 expression was remarkably decreased in tumor tissue samples from HCC patients, relative to matched nontumorous tissue samples, at the mRNA (p = 0.018) and protein level (p = 0.02). Similarly, immunohistochemical analysis showed that 53.4 % of samples had low TRIM3 protein expression. Clinicopathological analysis revealed that low TRIM3 expression was significantly correlated with tumor size (p = 0.034), histological grade (p < 0.001), serum AFP (p = 0.025), and TNM stage (p = 0.021). Furthermore, Kaplan–Meier survival analysis revealed that low TRIM3 expression was associated with poor survival in HCC patients. Finally, our multivariate Cox regression analysis showed that TRIM3 expression was an independent prognostic factor for overall survival of HCC patients. In conclusion, this study suggests that TRIM3 may play a significant role in HCC progression and acts as a valuable prognostic marker and potential therapeutic target for HCC.
Literature
1.
go back to reference Shariff MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W, Taylor-Robinson SD. Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 2009;3:353–67.PubMedCrossRef Shariff MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W, Taylor-Robinson SD. Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 2009;3:353–67.PubMedCrossRef
2.
go back to reference Yang S, Yan HL, Tao QF, Yuan SX, Tang GN, Yang Y, et al. Low CADM2 expression predicts high recurrence risk of hepatocellular carcinoma patients after hepatectomy. J Cancer Res Clin Oncol. 2014;140:109–16.PubMedCrossRef Yang S, Yan HL, Tao QF, Yuan SX, Tang GN, Yang Y, et al. Low CADM2 expression predicts high recurrence risk of hepatocellular carcinoma patients after hepatectomy. J Cancer Res Clin Oncol. 2014;140:109–16.PubMedCrossRef
3.
go back to reference Wu J, Du C, Lv Z, Ding C, Cheng J, Xie H, et al. The up-regulation of histone deacetylase 8 promotes proliferation and inhibits apoptosis in hepatocellular carcinoma. Dig Dis Sci. 2013;58:3545–53.PubMedCrossRef Wu J, Du C, Lv Z, Ding C, Cheng J, Xie H, et al. The up-regulation of histone deacetylase 8 promotes proliferation and inhibits apoptosis in hepatocellular carcinoma. Dig Dis Sci. 2013;58:3545–53.PubMedCrossRef
4.
go back to reference Pan QZ, Pan K, Zhao JJ, Chen JG, Li JJ, Lv L, et al. Decreased expression of interleukin-36alpha correlates with poor prognosis in hepatocellular carcinoma. Cancer Immunol Immunother. 2013;62:1675–85.PubMedCrossRef Pan QZ, Pan K, Zhao JJ, Chen JG, Li JJ, Lv L, et al. Decreased expression of interleukin-36alpha correlates with poor prognosis in hepatocellular carcinoma. Cancer Immunol Immunother. 2013;62:1675–85.PubMedCrossRef
5.
go back to reference Chen S, Chen J, Xi W, Xu W, Yin G. Clinical therapeutic effect and biological monitoring of p53 gene in advanced hepatocellular carcinoma. Am J Clin Oncol. 2014;37:24–9.PubMedCrossRef Chen S, Chen J, Xi W, Xu W, Yin G. Clinical therapeutic effect and biological monitoring of p53 gene in advanced hepatocellular carcinoma. Am J Clin Oncol. 2014;37:24–9.PubMedCrossRef
6.
go back to reference Wang KF, Pan W, Wang F, Wang GF, Madhava P, Pan HM, et al. Geometric optimization of a mathematical model of radiofrequency ablation in hepatic carcinoma. Asian Pac J Cancer Prev. 2013;14:6151–8.PubMedCrossRef Wang KF, Pan W, Wang F, Wang GF, Madhava P, Pan HM, et al. Geometric optimization of a mathematical model of radiofrequency ablation in hepatic carcinoma. Asian Pac J Cancer Prev. 2013;14:6151–8.PubMedCrossRef
7.
go back to reference Zhao JJ, Pan K, Li JJ, Chen YB, Chen JG, Lv L, et al. Identification of LZAP as a new candidate tumor suppressor in hepatocellular carcinoma. PLoS ONE. 2011;6:e26608.PubMedCentralPubMedCrossRef Zhao JJ, Pan K, Li JJ, Chen YB, Chen JG, Lv L, et al. Identification of LZAP as a new candidate tumor suppressor in hepatocellular carcinoma. PLoS ONE. 2011;6:e26608.PubMedCentralPubMedCrossRef
8.
go back to reference Zabaleta J, Aguinagalde B, Izquierdo JM, Bazterargui N, Laguna SM, Martin-Arruti M, et al. The presence of mutations in the K-RAS gene does not affect survival after resection of pulmonary metastases from colorectal cancer. ISRN Surg. 2014;2014:157586.PubMedCentralPubMedCrossRef Zabaleta J, Aguinagalde B, Izquierdo JM, Bazterargui N, Laguna SM, Martin-Arruti M, et al. The presence of mutations in the K-RAS gene does not affect survival after resection of pulmonary metastases from colorectal cancer. ISRN Surg. 2014;2014:157586.PubMedCentralPubMedCrossRef
9.
go back to reference Hu S, Wu X, Zhou B, Xu Z, Qin J, Lu H, et al. IMP3 combined with CD44s, a novel predictor for prognosis of patients with hepatocellular carcinoma. J Cancer Res Clin Oncol. 2014;140:883–93.PubMedCrossRef Hu S, Wu X, Zhou B, Xu Z, Qin J, Lu H, et al. IMP3 combined with CD44s, a novel predictor for prognosis of patients with hepatocellular carcinoma. J Cancer Res Clin Oncol. 2014;140:883–93.PubMedCrossRef
10.
go back to reference Yang Y, Fan YC, Gao S, Dou CY, Zhang JJ, Sun FK, et al. Methylated cysteine dioxygenase-1 gene promoter in the serum is a potential biomarker for hepatitis B virus-related hepatocellular carcinoma. Tohoku J Exp Med. 2014;232:187–94.PubMedCrossRef Yang Y, Fan YC, Gao S, Dou CY, Zhang JJ, Sun FK, et al. Methylated cysteine dioxygenase-1 gene promoter in the serum is a potential biomarker for hepatitis B virus-related hepatocellular carcinoma. Tohoku J Exp Med. 2014;232:187–94.PubMedCrossRef
11.
go back to reference Liu C, Xia Y, Jiang W, Liu Y, Yu L. Low expression of GABARAPL1 is associated with a poor outcome for patients with hepatocellular carcinoma. Oncol Rep. 2014;31:2043–8.PubMed Liu C, Xia Y, Jiang W, Liu Y, Yu L. Low expression of GABARAPL1 is associated with a poor outcome for patients with hepatocellular carcinoma. Oncol Rep. 2014;31:2043–8.PubMed
12.
go back to reference Xu X, Guo HJ, Xie HY, Li J, Zhuang RZ, Ling Q, et al. ZIP4, a novel determinant of tumor invasion in hepatocellular carcinoma, contributes to tumor recurrence after liver transplantation. Int J Biol Sci. 2014;10:245–56.PubMedCentralPubMedCrossRef Xu X, Guo HJ, Xie HY, Li J, Zhuang RZ, Ling Q, et al. ZIP4, a novel determinant of tumor invasion in hepatocellular carcinoma, contributes to tumor recurrence after liver transplantation. Int J Biol Sci. 2014;10:245–56.PubMedCentralPubMedCrossRef
14.
go back to reference Napolitano LM, Meroni G. TRIM family: pleiotropy and diversification through homomultimer and heteromultimer formation. IUBMB Life. 2012;64:64–71.PubMedCrossRef Napolitano LM, Meroni G. TRIM family: pleiotropy and diversification through homomultimer and heteromultimer formation. IUBMB Life. 2012;64:64–71.PubMedCrossRef
15.
go back to reference Nisole S, Stoye JP, Saib A. TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol. 2005;3:799–808.PubMedCrossRef Nisole S, Stoye JP, Saib A. TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol. 2005;3:799–808.PubMedCrossRef
16.
go back to reference El-Husseini AE, Vincent SR. Cloning and characterization of a novel RING finger protein that interacts with class V myosins. J Biol Chem. 1999;274:19771–7.PubMedCrossRef El-Husseini AE, Vincent SR. Cloning and characterization of a novel RING finger protein that interacts with class V myosins. J Biol Chem. 1999;274:19771–7.PubMedCrossRef
17.
go back to reference El-Husseini AE, Kwasnicka D, Yamada T, Hirohashi S, Vincent SR. BERP, a novel ring finger protein, binds to alpha-actinin-4. Biochem Biophys Res Commun. 2000;267:906–11.PubMedCrossRef El-Husseini AE, Kwasnicka D, Yamada T, Hirohashi S, Vincent SR. BERP, a novel ring finger protein, binds to alpha-actinin-4. Biochem Biophys Res Commun. 2000;267:906–11.PubMedCrossRef
18.
go back to reference Zoumpoulidou G, Broceno C, Li H, Bird D, Thomas G, Mittnacht S. Role of the tripartite motif protein 27 in cancer development. J Natl Cancer Inst. 2012;104:941–52.PubMedCrossRef Zoumpoulidou G, Broceno C, Li H, Bird D, Thomas G, Mittnacht S. Role of the tripartite motif protein 27 in cancer development. J Natl Cancer Inst. 2012;104:941–52.PubMedCrossRef
19.
go back to reference Zhou ZY, Yang GY, Zhou J, Yu MH. Significance of TRIM29 and beta-catenin expression in non-small-cell lung cancer. J Chin Med Assoc. 2012;75:269–74.PubMedCrossRef Zhou ZY, Yang GY, Zhou J, Yu MH. Significance of TRIM29 and beta-catenin expression in non-small-cell lung cancer. J Chin Med Assoc. 2012;75:269–74.PubMedCrossRef
20.
go back to reference Herquel B, Ouararhni K, Khetchoumian K, Ignat M, Teletin M, Mark M, et al. Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma. Proc Natl Acad Sci USA. 2011;108:8212–7.PubMedCentralPubMedCrossRef Herquel B, Ouararhni K, Khetchoumian K, Ignat M, Teletin M, Mark M, et al. Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma. Proc Natl Acad Sci USA. 2011;108:8212–7.PubMedCentralPubMedCrossRef
21.
go back to reference Marshall GM, Bell JL, Koach J, Tan O, Kim P, Malyukova A, et al. TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. Oncogene. 2010;29:6172–83.PubMedCentralPubMedCrossRef Marshall GM, Bell JL, Koach J, Tan O, Kim P, Malyukova A, et al. TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. Oncogene. 2010;29:6172–83.PubMedCentralPubMedCrossRef
22.
go back to reference 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. Am J Pathol. 2012;180:839–47.PubMedCrossRef 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. Am J Pathol. 2012;180:839–47.PubMedCrossRef
23.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
24.
go back to reference Raheja R, Liu Y, Hukkelhoven E, Yeh N, Koff A. The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity. Biochem J. 2014;458:537–45.PubMedCrossRef Raheja R, Liu Y, Hukkelhoven E, Yeh N, Koff A. The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity. Biochem J. 2014;458:537–45.PubMedCrossRef
25.
go back to reference Lim L, Balakrishnan A, Huskey N, Jones KD, Jodari M, Ng R, et al. MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer. Hepatology. 2014;59:202–15.PubMedCrossRef Lim L, Balakrishnan A, Huskey N, Jones KD, Jodari M, Ng R, et al. MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer. Hepatology. 2014;59:202–15.PubMedCrossRef
26.
go back to reference Dong YD, Cui L, Peng CH, Cheng DF, Han BS, Huang F. Expression and clinical significance of HMGB1 in human liver cancer: knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep. 2013;29:87–94.PubMed Dong YD, Cui L, Peng CH, Cheng DF, Han BS, Huang F. Expression and clinical significance of HMGB1 in human liver cancer: knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep. 2013;29:87–94.PubMed
27.
go back to reference Kashimoto K, Komatsu S, Ichikawa D, Arita T, Konishi H, Nagata H, et al. Overexpression of TRIM44 contributes to malignant outcome in gastric carcinoma. Cancer Sci. 2012;103:2021–6.PubMedCrossRef Kashimoto K, Komatsu S, Ichikawa D, Arita T, Konishi H, Nagata H, et al. Overexpression of TRIM44 contributes to malignant outcome in gastric carcinoma. Cancer Sci. 2012;103:2021–6.PubMedCrossRef
Metadata
Title
Decreased expression of TRIM3 is associated with poor prognosis in patients with primary hepatocellular carcinoma
Authors
Jie Chao
Xiao-Fei Zhang
Qiu-Zhong Pan
Jing-Jing Zhao
Shan-Shan Jiang
Ying Wang
Jian-Hua Zhang
Jian-Chuan Xia
Publication date
01-08-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 8/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0102-9

Other articles of this Issue 8/2014

Medical Oncology 8/2014 Go to the issue