Su Hao, Tang Yueheng, Nie Kexin, Wang Zhi, Wang Hongzhan, Dong Hui, Chen Gang
Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
Int J Gen Med. 2022 Feb 9;15:1349-1363. doi: 10.2147/IJGM.S341018. eCollection 2022.
Hepatocellular carcinoma (HCC) is one of the most common and mortality types of malignant tumors in the world. The Tripartite-Motif (TRIM) protein family consists of more than 80 proteins with E3 ubiquitin ligase activity. Increasing studies have found that TRIM family proteins play an extremely important role in the occurrence and development of tumors. However, the expression and prognostic values of TRIMs in HCC have not been clarified.
We used bioinformatic methods to explore the potential function of TRIM family genes in the HCC. Web servers ONCOMINE, UALCAN, GEPIA, cBioPortal, STRING, DAVID 6.8 and TIMER were used in this research.
We screened TRIM1-76 and found the expressions of TRIM6, TRIM11, TRIM16, TRIM18(MID1), TRIM24, TRIM28, TRIM31, TRIM37, TRIM45, TRIM52, TRIM59, TRIM66 were significantly changed in HCC. Among them, TRIM24, TRIM28, TRIM37, TRIM45 and TRIM59 had significant effects on pathological stages, overall survival and disease free survival. Functions of these genes are primarily related to transcriptional misregulation in cancer, p53 signaling pathway, alcoholism and viral carcinogenesis, FoxO signal pathway, PI3K-AKT pathway, cell cycle, microRNAs in cancer. Our results showed the significant correlation between TRIMs expression and infiltration of innate immune cells (macrophages, neutrophils, and dendritic cells).
Our result provides novel insights into the function of TRIM family genes, which may be used as potential references for drug targets and accurate survival predictions in patients with HCC.
肝细胞癌(HCC)是全球最常见且致死率最高的恶性肿瘤类型之一。三联基序(TRIM)蛋白家族由80多种具有E3泛素连接酶活性的蛋白质组成。越来越多的研究发现,TRIM家族蛋白在肿瘤的发生和发展中起着极其重要的作用。然而,TRIMs在HCC中的表达及预后价值尚未明确。
我们使用生物信息学方法探索TRIM家族基因在HCC中的潜在功能。本研究使用了在线服务器ONCOMINE、UALCAN、GEPIA、cBioPortal、STRING、DAVID 6.8和TIMER。
我们筛选了TRIM1 - 76,发现TRIM6、TRIM11、TRIM16、TRIM18(MID1)、TRIM24、TRIM28、TRIM31、TRIM37、TRIM45、TRIM52、TRIM59、TRIM66在HCC中的表达有显著变化。其中,TRIM24、TRIM28、TRIM37、TRIM45和TRIM59对病理分期、总生存期和无病生存期有显著影响。这些基因的功能主要与癌症中的转录失调、p53信号通路、酒精中毒和病毒致癌作用、FoxO信号通路、PI3K - AKT通路、细胞周期、癌症中的微小RNA有关。我们的结果显示TRIMs表达与先天免疫细胞(巨噬细胞、中性粒细胞和树突状细胞)的浸润之间存在显著相关性。
我们的结果为TRIM家族基因的功能提供了新的见解,这可能为HCC患者的药物靶点和准确的生存预测提供潜在参考。