Abstract
The TRIM family is associated with the membrane, and its involvement in the progression, growth, and development of various cancer types has been researched extensively. However, the role played by the TRIM5 gene within this family has yet to be explored to a great extent in terms of hepatocellular carcinoma (HCC). The data of patients relating to mRNA expression and the survival rate of individuals diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA) database. UALCAN was employed to examine the potential link between TRIM5 expression and clinicopathological characteristics. In addition, enrichment analysis of differentially expressed genes (DEGs) was conducted as a means of deciphering the function and mechanism of TRIM5 in HCC. The data in the TCGA and TIMER2.0 databases was utilized to explore the correlation between TRIM5 and immune infiltration in HCC. WGCNA was performed as a means of assessing TRIM5-related co-expressed genes. The "OncoPredict" R package was also used for investigating the association between TRIM5 and drug sensitivity. Finally, qRT-PCR, Western blotting (WB) and immunohistochemistry (IHC) were employed for exploring the differential expression of TRIM5 and its clinical relevance in HCC. According to the results that were obtained from the vitro experiments, mRNA and protein levels of TRIM5 demonstrated a significant upregulation in HCC tissues. It is notable that TRIM5 expression levels were found to have a strong association with the infiltration of diverse immune cells and displayed a positive correlation with several immune checkpoint inhibitors. The TRIM5 expression also displayed promising clinical prognostic value for HCC patients.
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The datasets presented in this study can be found in onlinerepositories. The names ofthe repository/repositories and accessionnumber(s) can be found in the article/Supplementary Material.
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Acknowledgements
We thank the research team members for their assistance and direction, and professor Ai-Wu Ke (Liver Cancer Institute, Zhongshan Hospital, Fudan University) for assistance with the sample and phenotype information collection.
Funding
This work was funded by the National Natural Science Foundation of China (Grant No. 81871909; 82203716), the “13th five-year Plan” Science and Education strong Health Project Innovation team of Yangzhou (LJRC20181; YZCXTD201801), Provincial-level discipline leader of the NJPH (DTRA202214), Cross-cooperation special projects of the NJPH (YJCHZ-2021–08), Beijing iGanDan Foundation (GDXZ-08–19), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22_3568), Yangzhou Key Social Development Project (YZ2022093).
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(I) Conceptualization: D Bai, C Zhang, H Liu, Y Tang; (II) Study design: D Bai, C Zhang, R Peng; (III) Acquisition of data: H Liu, J Cao, J Zhang, G Wu, D Tu; (IV) Execution: S Jin, R Liu, G Jiang, Q Wang, B Su and A Wang; (V) Analysis and interpretation H Liu, Y Tang, Q Peng, C Chen. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
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Supplementary file1 Supplementary Fig. 1 Diagnostic ROC curves to distinguish HCC tissues and normal tissues based on the TRIM5 expression levels. (TIF 546 KB)
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Supplementary file2 Supplementary Fig. 2 Correlation between TRIM5 expression and immune checkpoint gene expression in HCC. (TIF 5463 KB)
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Liu, H., Tang, Y., Zhang, J. et al. TRIM5 as a promising diagnostic biomarker of hepatocellular carcinoma: integrated analysis and experimental validation. Funct Integr Genomics 24, 63 (2024). https://doi.org/10.1007/s10142-024-01339-6
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DOI: https://doi.org/10.1007/s10142-024-01339-6