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

Abstract

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 < 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.

METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expression

“…High LSM4 expression enhanced ovarian cancer cell proliferation, metastasis and glycolysis 28 . LSM4 had increased expression in hepatocellular carcinoma and could serve as a diagnostic marker, which upregulation contributed to cell malignant behaviors 29,30 . Although LSM4 has been shown to be oncogenic in many cancers, its role in NSCLC progression has not been explored.…”

Pan-cancer analysis revealed the significance of the GTPBP family in cancer

“…The complex mechanisms in cancer cells have been extensively studied by researchers, but the available information is still far from sufficient [ 8 ]. The highly metabolically active nature of cancer, the over-activation of growth signals, and the unrestricted replication of cells have led us to ask the following questions: what on earth promotes the occurrence of cancer [ 9 – 11 ]? How do you kill cancer cells by inhibiting these mechanisms?…”

Significance of Spliceosome-Related Genes in the Prediction of Prognosis and Treatment Strategies for Lung Adenocarcinoma

“…LSM4 is involved in the disease progression of pancreatic cancer by mediating the formation of U4/U6 snRNP [ 33 , 34 ]. Recent research by Chen et al suggested that LSM4 may affect the growth and transfer of HCC cells by regulating key pathways such as cell cycles, adhesive plaques, and metabolic-related pathways [ 35 ]. At present, the mechanism of action of LSM4 and LSM5 in lung cancer has not been reported.…”