DCUN1D5 as a New Biomarker and Regulator of Fatty Acid Metabolism in Hepatocellular Carcinoma

Tong Wang,1,* Tianrun Yang,1,* Tianze Wang,1 Ziming Wang,1 Pinsheng Han,2 Yi Bai,3 Yamin Zhang31First Central Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3Tianjin First Central Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yamin Zhang, Tianjin First Central Hospital, Tianjin, People’s Republic of China, Email 5020200824@nankai.edu.cn Yi Bai, Tianjin First Central Hospital, Tianjin, People’s Republic of China, Email baiyipumch@sina.comBackground: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, with limited reliable biomarkers for early diagnosis and prognosis. In this study, we explored the role of DCUN1D5, a potential biomarker, in HCC.Methods: We performed integrated bioinformatics analyses of publicly available HCC datasets, including TCGA, GEO, and ICGC, followed by in vitro experiments on HCC cell lines to validate our findings.Results: DCUN1D5 expression was significantly elevated in HCC tissues compared to normal liver tissues. High DCUN1D5 levels were associated with poor prognosis and advanced tumor stage in HCC patients. Additionally, bioinformatics analysis revealed a correlation between DCUN1D5 expression levels and both immune infiltration and immunotherapy response in hepatocellular carcinoma. Functional assays revealed that DCUN1D5 knockdown inhibited cell proliferation, migration, and invasion in HCC cells. Mechanistically, Enrichment analysis revealed significant correlations between DCUN1D5 and multiple biological pathways; specifically, we observed a negative correlation between the expression level of DCUN1D5 and fatty acid metabolism. Further cellular experiments demonstrated that knockdown of DCUN1D5 can induce accumulation of free fatty acids in hepatocellular carcinoma cells.Conclusion: In summary, our study identified DCUN1D5 as a potential biomarker for poor prognosis in HCC, high expression of DCUN1D5 are closely associated with tumor invasion and proliferation. Knockdown of DCUN1D5 was found to inhibit the proliferation, migration, and invasion of HCC cells and increases its free fatty acid accumulation. These studies suggest new possibilities for treatment strategies for HCC.Keywords: DCUN1D5, HCC, fatty acid metabolism, biomarkers, prognosis, immunotherapy