Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.
The First School of Clinical Medicine of Nanchang University, Jiangxi Medical College of Nanchang University, Nanchang, Jiangxi, People's Republic of China.
Medicine (Baltimore). 2023 Jun 9;102(23):e34012. doi: 10.1097/MD.0000000000034012.
Tripartite motif-containing protein 21 (TRIM21), a member of the ubiquitin ligase family, makes a significant contribution to the ubiquitination of multiple tumor marker proteins associated with tumor cell proliferation, metastasis and selective apoptosis. As the research further develops, an increasing number of studies have manifested that the TRIM21 expression level can be considered an indicator of cancer prognosis. However, the interrelationship between TRIM21 and multiple forms of carcinogens has not been demonstrated in a meta-analysis.
We performed a systematic literature retrieval in various electronic databases including PubMed, Embase, Web of Science, Wanfang and China National Knowledge Infrastructure. Besides, the hazard ratio (HR) and the pooled relative risk (RR) were integrated in the assessment of cancer incidence and cancer mortality by Stata SE15.1. Additionally, we used an online database based on The Cancer Genome Atlas (TCGA) to further validate our results.
A total of 17 studies were included, totaling 7239 participants. High expression of TRIM21 was significantly correlated with better OS (HR = 0.74; 95% CI: 0.57-0.91; P < .001) and progression-free survival (PFS) (HR = 0.66; 95% CI: 0.42-0.91; P < .001). We found that high TRIM21 expression predicted significant impact on clinical characteristics like decreased lymph node metastasis (RR = 1.12; 95% CI: 0.97-1.30; P < .001), tumor stage (RR = 1.06; 95% CI: 0.82-1.37; P < .001) and tumor grade (RR = 1.07; 95% CI: 0.56-2.05; P < .001). However, TRIM21 expression had no significant impact on other clinical characteristics such as age (RR = 1.06; 95% CI: 0.91-1.25; P = .068), sex (RR = 1.04; 95% CI: 0.95-1.12; P = .953), or tumor size (RR = 1.14; 95% CI: 0.97-1.33; P = .05). Based on the Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool, TRIM21 was significantly downregulated in 5 cancers while significantly upregulated in 2 cancers, and the descending expression of TRIM21 predicted shorter OS in 5 cancers, worse PFS in 2 malignancies, while the elevated expression of TRIM21 predicted shorter OS and worse PFS in 2 carcinomas.
TRIM21 could serve as a new biomarker for patients with solid malignancies and could be a potential therapeutic target for patients.
三结构域蛋白 21（TRIM21）是泛素连接酶家族的成员，对与肿瘤细胞增殖、转移和选择性凋亡相关的多种肿瘤标志物蛋白的泛素化有重要贡献。随着研究的进一步发展，越来越多的研究表明 TRIM21 的表达水平可以作为癌症预后的指标。然而，TRIM21 与多种形式的致癌物质之间的相互关系尚未在荟萃分析中得到证明。
我们在各种电子数据库中进行了系统的文献检索，包括 PubMed、Embase、Web of Science、万方和中国知网。此外，我们使用基于癌症基因组图谱（TCGA）的在线数据库进一步验证了我们的结果。我们使用 Stata SE15.1 对癌症发病率和癌症死亡率进行了风险比（HR）和合并相对风险（RR）的综合评估。
共纳入 17 项研究，总计 7239 名参与者。TRIM21 的高表达与更好的总生存期（HR = 0.74；95%CI：0.57-0.91；P <.001）和无进展生存期（PFS）（HR = 0.66；95%CI：0.42-0.91；P <.001）显著相关。我们发现，TRIM21 高表达预示着对临床特征有显著影响，如淋巴结转移减少（RR = 1.12；95%CI：0.97-1.30；P <.001）、肿瘤分期（RR = 1.06；95%CI：0.82-1.37；P <.001）和肿瘤分级（RR = 1.07；95%CI：0.56-2.05；P <.001）。然而，TRIM21 表达对其他临床特征如年龄（RR = 1.06；95%CI：0.91-1.25；P =.068）、性别（RR = 1.04；95%CI：0.95-1.12；P =.953）或肿瘤大小（RR = 1.14；95%CI：0.97-1.33；P =.05）没有显著影响。基于基因表达谱交互分析（GEPIA）在线分析工具，TRIM21 在 5 种癌症中显著下调，在 2 种癌症中显著上调，TRIM21 的下调表达预示着 5 种癌症的总生存期缩短，2 种癌症的无进展生存期缩短，而 TRIM21 的上调表达预示着 2 种癌症的总生存期和无进展生存期缩短。
TRIM21 可以作为实体恶性肿瘤患者的新生物标志物，并可能成为患者的潜在治疗靶点。
