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Background:  Hepatocellular carcinoma (HCC) is a solid tumor with high recurrence rate and high mortality. It is crucial to discover available biomarkers to achieve early diagnosis and improve the prognosis. The effect of  LSM4  in HCC still remains unrevealed. Our study is dedicated to exploring the expression of  LSM4  in HCC, demonstrating its clinical significance and potential molecular mechanisms.   Methods:  Clinical information and LSM4 expression values of HCC were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Survival analysis and receiver operating characteristic (ROC) curve analysis were applied to evaluate the prognostic and diagnostic significance of  LSM4 . Calculating pooled standardized mean difference (SMD) and performing summary receiver operating characteristic (sROC) curve analysis to further determine its expression status and diagnostic significance.  LSM4 -related co-expressed genes (CEGs) were obtained and explored their clinical significance in HCC.  LSM4 -associated pathways were identified through Gene set enrichment analysis (GSEA).   Results:  Up-regulated  LSM4  was detected in HCC tissues (SMD = 1.56, 95% CI: 1.29–1.84) and overexpressed  LSM4  had excellent distinguishing ability (AUC = 0.91, 95% CI: 0.88–0.93).  LSM4  was associated with clinical stage, tumor grade, and lymph node metastasis status ( p  &amp;lt; 0.05). Survival analysis showed that high  LSM4  expression was related to poor overall survival (OS) of HCC patients. Cox regression analysis suggested that high  LSM4  expression may be an independent risk factor for HCC. We obtained nine up-regulated CEGs of  LSM4  in HCC tissues, and six CEGs had good prognostic and diagnostic significance. GSEA analysis showed that up-regulated  LSM4  was closely related to the cell cycle, cell replication, focal adhesion, and several metabolism-associated pathways, including fatty acid metabolism.   Conclusion:  Overexpressed  LSM4  may serve as a promising diagnostic and prognostic biomarker of HCC. Besides,  LSM4  may play a synergistic effect with CEGs in promoting the growth and metastasis of HCC cells  via  regulating crucial pathways such as cell cycle, focal adhesion, and metabolism-associated pathways.

Clinical Significance and Potential Role of LSM4 Overexpression in Hepatocellular Carcinoma: An Integrated Analysis Based on Multiple Databases