ANP32 Family as Diagnostic, Prognostic, and Therapeutic Biomarker Related to Immune Infiltrates in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes ANP32A, ANP32B, and ANP32E, are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that ANP32A, ANP32B, and ANP32E were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. ANP32A, ANP32B, and ANP32E had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that ANP32A, ANP32B, and ANP32E were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of ANP32B and ANP32E to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.

Integrated analysis of single-cell and bulk RNA sequencing data reveals a CD8+ T cells signature predicting prognosis and immunotherapy response in hepatocellular carcinoma

“…In addition, we compared the e cacy of multiple machine learning algorithms by C-index to construct the best consensus prognostic model and validated the genes in the model (ANP32B, KIF2C, and RAN) by mIHC. Additionally, Liu et al found that high ANP32B expression correlated with higher pathological stages of HCC, and knockdown of ANP32B would contribute to delay the progression of HCC [33]. A previous study found signi cantly higher expression levels of RAN in HCC tissues, which suggests that high expression of RAN is associated with poor prognosis in HCC [34].…”

ANP32B promotes colorectal cancer cell progression and reduces cell sensitivity to PRAP1 inhibitor through up-regulating HPF1

“…Higher ANP32B mRNA expression is a marker of poor prognosis in patients with breast cancer [ 17 ], whereas ANP32B was found to suppress breast cancer tumor growth [ 18 ]. ANP32B mRNA and protein are highly expressed in hepatocellular carcinoma (HCC), with these levels of expression associated with tumor cell proliferation and invasion, suggesting that ANP32B is pro-oncogenic in HCC [ 19 ]. In contrast, ANP32B downregulation was found to have antiapoptotic effects in HCC, whereas ANP32B upregulation did not lead to HCC apoptosis and functioned as a cell cycle progression factor in HCC [ 20 ].…”

“…The ANP32B protein was found to be located in the nucleus and be associated with brain development by regulating the proliferation of neuronal cells [ 13 ]. ANP32B was shown to be important for cell proliferation, apoptosis, and cell cycle progression [ 14 , 15 ], and to participate in various types of cancer, including leukemia [ 14 , 16 ], breast cancer [ 17 , 18 ], hepatocellular carcinoma [ 19 , 20 ], pancreatic adenocarcinoma [ 21 ] and thyroid carcinoma [ 22 ]. Although ANP32B expression was also found to be upregulated in patients with CRC [ 23 ], the precise function of ANP32B in CRC remains to be determined.…”