Effect of SLC12A4 Gene Expression on Lung Squamous Cell Carcinoma Based on Bioinformatic Analysis
HU Yunlong
ZHANG Shuliu
YU Aoran
YANG Kairui
Abstract：Objective To investigate the expression,bioinformatic function,and clinical significance of solute carrier family 12 member 4(SLC12A4)in lung squamous cell carcinoma(LUSC).Methods A total of 551 samples of SLC12A4 mRNA expression,methylation,and clinicopathological data were downloaded from the UCSC Xena online database(The Cancer Genome Atlas-LUSC dataset).Among these,49 normal samples and 501 LUSC samples contained SLC12A4 expression data,including 49 pairs of matched expression data(normal lung tissue vs LUSC tissue);378 samples contained both SLC12A4 methylation data and expression data,including 40 pairs of matched methylation data.The 501 LUSC samples were divided into SLC12A4 high-expression group(251 cases)and SLC12A4 low-expression group(250 cases)based on whether their SLC12A4 expression level was above the median.Differences in SLC12A4 expression and methylation between normal lung tissue and LUSC tissue were compared.The correlations between SLC12A4 expression and methylation,as well as between expression and clinicopathological features,were analyzed.Using the Xiantao Academic Online tool,enrichment analysis of SLC12A4 co-expressed genes,Kaplan-Meier survival analysis,and time-dependent ROC curve analysis were performed within The Cancer Genome Atlas-LUSC dataset,and the results were visualized.Results In LUSC tissues,SLC12A4 expression was significantly downregulated compared with normal lung tissues(P<0.01).The methylation β-values at sites cg08958168,cg05261851,cg26912222,and cg09086087 were significantly higher in LUSC tissues than in normal tissues(P<0.01)and were negatively correlated with SLC12A4 expression(P<0.01).Enrichment analysis of SLC12A4 co-expressed genes indicated that SLC12A4 may be involved in regulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway.The proportion of patients with low SLC12A4 expression was lower in those with pathological N stage N0 than in those with N1/N2/N3 stages(46.1%vs 58.0%,P<0.05).Kaplan-Meier survival analysis and time-dependent ROC curve analysis showed that high SLC12A4 expression was closely associated with poor prognosis in LUSC patients.Conclusion SLC12A4 expression is downregulated in LUSC tissues and may be regulated by epigenetic mechanisms.SLC12A4 may affect the progression of LUSC by regulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway,thereby influencing patient prognosis.SLC12A4 has the potential to serve as a biomarker for the diagnosis,prognosis,and treatment of LUSC.
Keywords：lung squamous cell carcinomasolute carrier family 12 member 4methylationprognostic valuegene enrichment analysis
Publication Date：2025-10-20
Online Publishing Date：2025-10-28(First online date of this platform, not the publication date of the document)
Pages：7( 174-180 )