Integrative multiomics dissection of LSM7 as a prognostic biomarker and therapeutic target in hepatocellular...

ObjectiveHepatocellular carcinoma (HCC) has a poor prognosis, necessitating novel biomarkers. The role of LSM7 (Like-Sm protein 7), an RNA-binding protein, in HCC remains unclear.MethodsWe employed a multiomics strategy using transcriptomic data from TCGA, GTEx, GEO, and ICGC to evaluate LSM7's expression and prognostic value. A protein-protein interaction (PPI) network was constructed via STRING, followed by Gene Ontology/KEGG/Gene Set Enrichment Analysis (GSEA) functional enrichment analysis. The relationship between LSM7 and the immune infiltration landscape was assessed using single-sample GSEA (ssGSEA) and the TISCH single-cell database. Drug sensitivity was analyzed using Genomics of Drug Sensitivity in Cancer, and structure-based virtual screening was performed on the ZINC library to identify potential LSM7 inhibitors. Key findings were validated in clinical samples and MHCC97H cells and Huh-7 cells using Western blot, IHC, and MTT assays.ResultsLSM7 was significantly overexpressed in HCC, correlating with adverse clinicopathological features (higher histological grade, elevated AFP levels, vascular invasion) and shorter overall survival, identifying it as an independent risk factor. Functionally, LSM7 was implicated in processes such as hormone regulation. Immune analysis revealed that high LSM7 expression was associated with altered immune cell abundance, upregulation of immune checkpoints, and a higher Tumor Immune Dysfunction and Exclusion score, suggesting a role in immune evasion. The high-LSM7 group showed increased sensitivity to drugs like sorafenib. Virtual screening identified Velpatasvir as a top LSM7-targeting candidate, with in vitro validation confirming that it inhibits MHCC97H cells and Huh-7 cells proliferation and downregulates LSM7 protein in a concentration- and time-dependent manner.ConclusionsBy integrating multiomics strategy and experimental validation, this study suggests that LSM7 may play a role in HCC progression and influence the tumor immune microenvironment. LSM7 may serve as a potential biomarker and therapeutic target, and Velpatasvir appears to be a candidate agent worthy of further investigation.