Multi-Omics Analysis Reveals DNASE1L3 in Hepatocellular Carcinoma Prognosis, Immune Microenvironment, and Immunotherapy Response

INTRODUCTION: Hepatocellular Carcinoma (HCC) is the most prevalent primary liver cancer, characterized by its poor prognosis. Deoxyribonuclease 1-like 3 (DNASE1L3), a member of the deoxyribonuclease 1 family, has been implicated in various human cancers, but its specific role in HCC remains unclear. METHODS: By integrating transcriptomic and proteomic datasets, DNASE1L3 was identified as significantly associated with HCC through WGCNA and Lasso regression analysis. Subsequently, the clinical diagnostic significance of DNASE1L3 was confirmed using data from TCGA. Additionally, we evaluated immune treatment responsiveness by analyzing Tumor Mutation Burden (TMB) values, Tumor Immune Dysfunction and Exclusion (TIDE) scores, and the expression of immune checkpoint genes. Furthermore, DNASE1L3 expression in HCC was examined through single-cell RNA sequencing (scRNA-seq) analysis using the TISCH 2.0 database. RESULTS: DNASE1L3 expression was significantly reduced in HCC and associated with a poor prognosis. The DNASE1L3low group exhibited higher TMB values and expression of immune checkpoint genes, along with a lower TIDE score, suggesting a greater likelihood of successful immunotherapy. Moreover, scRNA-seq analysis revealed that DNASE1L3 was predominantly expressed in HCC endothelial cells, myeloid cells, and innate lymphoid cells. DISCUSSION: Our findings indicate that DNASE1L3 may be a potential biomarker for both predicting prognosis and assessing the effectiveness of immunotherapy, thus providing significant information for forecasting clinical results and responses to immunotherapy in HCC. CONCLUSION: The findings of this research could facilitate early detection and propose possible therapeutic targets for HCC.