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

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.

Tripartite motif-containing 3 (TRIM3) inhibits tumor growth and metastasis of liver cancer

“…Contrarily, silencing TRIM3 promoted cell motility. These findings were consistent with the results of our clinicopathologic analysis, which showed that low TRIM3 expression was significantly associated with advanced tumor stage [ 25 ]. Furthermore, we performed in vivo metastasis assay in nude mice to investigate whether TRIM3 overexpression could alter the in vivo metastatic ability of liver cancer cells.…”

“…TRIM3 overexpression in HepG2 and Bel-7402 cells significantly delayed tumor growth in mice. These results were in line with our clinical findings that the low level of TRIM3 was significantly associated with large tumors [ 25 ]. Consistent with our results, previous studies also demonstrated that TRIM3 overexpression inhibited glioma cell proliferation and tumor growth [ 27 , 28 ].…”

“…In our previous study [ 25 ], we found that TRIM3 expression was significantly down-regulated in most HCC tumor tissues, compared with corresponding noncancerous tissues. We also found that low TRIM3 expression was an independent indicator of poor prognosis in HCC patients.…”

“…This observation indicates that the TRIM3 may be a novel tumor-related gene. Our previous study indicated that TRIM3 expression was down-regulated in HCC at both the mRNA and protein levels and that low TRIM3 expression was associated with an unfavorable prognosis [ 25 ]. To elucidate the potential role of TRIM3 in the development of liver cancer, we investigated the functions of TRIM3 in liver cancer cell lines.…”

Multifaceted Roles of TRIM Proteins in Colorectal Carcinoma

“…Interestingly, opposing effects of aberrant TRIM expression on carcinogenesis can occur ranging from oncogenic to mainly tumor-suppressive effects depending on the protein targeted by the respective TRIM. While the majority of TRIM proteins have been assigned to act mainly as oncogenes due to the bad prognosis and outcome of patients with high tissue expression levels of the corresponding TRIM protein, only a few members including TRIM3 [ 33 ], TRIM8 [ 34 ], TRIM15 [ 35 ], TRIM45 [ 36 ], TRIM58 [ 37 ], and TRIM68 [ 38 ] can elicit tumor suppressive activities. In accordance, some of these tumor suppressive TRIM members are downregulated in CRC [ 39 ].…”