Abstract

Purpose: The expression and clinical value of zinc finger protein 2 gene (ZIC2) in hepatocellular carcinoma (HCC) were analyzed by mining gene information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.Methods: Gene chip data sets were retrieved from GEO and TCGA and screened for differentially expressed genes in HCC. Gene expression profile interaction analysis (GEPIA) and Kaplan–Meier curves were used to analyze the relationship between differentially expressed genes (DEGs) and survival and prognosis in patients with HCC. Moreover, the Genecards database was used to extract ZIC2-related proteins and to analyze the physiological process of protein enrichment. Furthermore, the relationships between ZIC2 gene and tumor cell immune invasion and that between immune cell infiltration and the 5-year survival rate were studied using the tumor immune evaluation resource (TIMER) database.Results: Datasets from GEO and TCGA revealed that ZIC2 was differentially expressed in HCC tissues and normal tissues (P<0.05). High ZIC2 expression was associated with overall survival (OS) and progress-free survival in HCC patients. Overall, 25 ZIC2 related proteins, including Gli3, PRKDC, and rnf180 were identified and protein enrichment analysis indicated these were associated with four types of cell components, six types of cell functions, and eight types of biological processes. ZIC2 was positively correlated with immune infiltration cells in patients with HCC, and higher expression of ZIC2 mRNA CD4+T cells is associated with a better 5-year survival.Conclusion: ZIC2 gene may be used as an immune response marker in liver cancer to predict the prognosis of HCC.

Highlights

  • Zinc finger protein zinc finger protein 2 gene (ZIC2) is encoded by the ZIC2 gene and can interact with DNA and proteins [1]

  • 1503 and 2288 differentially expressed gene (DEG) were identified from GSE144269 and The Cancer Genome Atlas (TCGA) datasets, and 386 genes were found to be common to both data sets

  • These findings indicated that ZIC2 up-regulation could promote liver cancer growth presumably via cell cycle alteration and regulation of cell division

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Summary

Introduction

Zinc finger protein ZIC2 is encoded by the ZIC2 gene and can interact with DNA and proteins [1]. The encoded protein acts as a transcription inhibitor and can regulate the tissue-specific expression of dopamine receptor D1. Gene ontology (GO) annotations related to ZIC2 gene include DNA-binding transcription factor activity and chromatin DNA binding [3]. Recent studies have reported that ZIC2 functions as an oncogene in various cancers [4]. Numerous studies have found that the ZIC2 gene is expressed abnormally in a various solid tumors including breast cancer [5], nasopharyngeal cancer [6], and cervical cancer [7]. Tumor immunotherapy, characterized by immunosuppressive checkpoint inhibitors, has represented an important breakthrough, and has thereby introduced novel therapies for the treatment of cancer in recent years [8].

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