Expression and prognostic value of LYPLA2 in hepatocellular carcinoma and its correlation with the immune microenvironment
MU Ning
ZHOU Haiwei
FU Junhui
ZHENG Shuang
WANG Caizheng
Abstract：Objective To systematically evaluate the expression characteristics,prognostic value,and related biological functions of acyl-protein thioesterase 2(LYPLA2)in hepatocellular carcinoma(HCC),and to explore its potential application value in HCC diagnosis and treatment.Methods Transcriptomic data from 374 HCC tissues and 50 normal liver tissues in the Cancer Genome Atlas(TCGA)database were integrated to analyze the differential expression of LYPLA2,its correlation with prognosis and clinicopathological features.The CIBERSORT algorithm was used to assess immune cell infiltration,and Gene Set Enrichment Analysis(GSEA)was employed to screen LYPLA2-related signaling pathways.Fresh cancer tissues and adjacent non-cancerous tissues from 10 HCC patients who underwent surgical treatment at Taizhou First People's Hospital between October 2022 and October 2023 were collected.Immunohistochemical staining was used to verify the differential expression of the LYPLA2 protein.The Kaplan-Meier method was used for survival analysis,and Cox proportional hazards regression models were applied to evaluate prognostic factors.Results Analysis based on TCGA data showed that the mRNA expression level of LYPLA2 was significantly higher in HCC tissues compared to normal liver tissues(P＜0.001).Immunohistochemical staining results from clinical samples further confirmed that LYPLA2 protein expression was higher in HCC tissues than in adjacent tissues,approximately 2.8 times higher(histochemistry score:52.3±8.7 vs.18.6±5.2,P＜0.001).The median overall survival of patients in the high LYPLA2 expression group was significantly shortened by 50.9 months compared to the low LYPLA2 expression group(33.5 months vs.84.4 months,HR=2.37,95％CI=1.66-3.40,P＜0.001).The receiver operating characteristic curve(ROC)curve analysis indicated that LYPLA2 had good predictive efficacy for the 3-year survival rate of HCC patients(AUC=0.844).LYPLA2 expression significantly increased with higher pathological grade and elevated alpha-fetoprotein(AFP)levels(P＜0.05).Univariate Cox regression analysis showed that stage,pathological T stage,pathological M stage,and LYPLA2 expression were all factors affecting the prognosis of HCC patients(P＜0.05).Multivariate Cox regression analysis further confirmed that LYPLA2 expression was an independent prognostic factor for HCC(HR=2.124,95％CI:1.313-3.434,P=0.002).Correlation analysis revealed that high LYPLA2 expression was positively correlated with the infiltration levels of CD56+natural killer cells(r=0.371),macrophages(r=0.133),Th2 cells(r=0.191),and follicular helper T cells(r=0.128),and was co-expressed with immunomodulatory and immunosuppressive molecules.GSEA indicated that LYPLA2-related genes were significantly enriched in pathways such as DNA repair inhibition and metabolic reprogramming.Conclusion LYPLA2 is upregulated in HCC and serves as an independent adverse prognostic factor.Its mechanism may be related to reshaping the tumor immunosuppressive microenvironment.Targeting LYPLA2 holds promise as a novel strategy for HCC immunotherapy.
Keywords：hepatocellular carcinomaacyl protein thioesterase 2prognosisimmune checkpointtumor microenvironment
Publication Date：2026-02-28
Online Publishing Date：2026-04-01(First online date of this platform, not the publication date of the document)
Pages：7( 148-154 )