An analysis of pan-cancer studies on the potential prognostic and immunotherapy biomarker of acidic nuclear phosphoprotein 32A in cancer
Objective:To evaluate the association of acidic nuclear phosphoprotein 32A(ANP32A)with survival prognosis and immunological regulation of various types of human cancer.Methods:The differential expression analysis of ANP32A was based on genotype-tissue expression(GTEx),cancer cell line encyclopedia(CCLE)and the cancer genome atlas(TCGA)database.COX regression test and Kaplan-Meier test were used to analyze the prognosis.Spearman test was used for correlation analysis.The gene ontology(GO)and the Kyoto encyclopedia of genes and genomes(KEGG)were used to enrich the relevant signaling pathways.Immunohistochemistry(IHC)staining and western blot(WB)expression of ANP32A and RNA-binding protein human antigen R(HuR)in non-small cell lung carcinoma(NSCLC)were assessed,and the correlations between the two were also analyzed.Results:In most cancers,the expression of ANP32A in tumor tissues was significantly higher than that in normal tissues.COX regression analysis showed that the expression of ANP32A in about 10 cancers was significantly correlated with prognosis,and high expression of ANP32A in 7 cancer types was associated with adverse overall survival,including acute myeloid leukemia,adrenocortical carcinoma and acute lymphoblastic leukemia in remission stage,et al.However,in three cancers,such as glioblastoma multiforme low-grade glioma,kidney renal clear cell carcinoma,and thymoma,patients with high expression of ANP32A had a good prognosis.Further analysis showed that the expression of ANP32A was significantly correlated with multiple immune checkpoints and immune-related genes.In addition,ANP32A was also closely related to immune cell infiltration,RNA modification,genomic heterogeneity and tumor stemness in the tumor microenvironment.GO and KEGG analysis showed that ANP32A was involved in the regulation of messenger RNA splicing,ribonucleoprotein complex biogenesis and histone modification.IHC data showed a positive correlation between the expression of ANP32A and HuR in NSCLC.WB results confirmed that ANP32A could induce the expression of HuR in human NSCLC A549 cell line,suggesting that ANP32A may be involved in physiological processes such as messenger RNA splicing through regulation of HuR.Conclusions:ANP32A is a novel tumor prognostic predictor,and plays an important role in immunological regulation of tumor immune cell invasion,RNA modification,genomic heterogeneity,tumor dryness,and mRNA splicing processing.