Abstract

Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) is involved in the deacetylation of p53 in regulating cell cycle and is associated with cancers at the molecular level. In this study, we evaluated the prognostic value in hepatocellular carcinoma (HCC) based on data from The Cancer Genome Atlas (TCGA) database. Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate the relationship between DNTTIP1 expression and clinicopathological features. Cox regression and the Kaplan–Meier method were adopted to evaluate prognosis-related factors. Gene set enrichment analysis (GSEA) was performed to identify the key pathways related to DNTTIP1. The correlations between DNTTIP1 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis (ssGSEA). DNTTIP1 was found to be upregulated with amplification in tumor tissues in multiple HCC cohorts. High DNTTIP1 expression was associated with poorer overall survival (OS) and disease-free survival (DFS). GSEA suggested that DNTTIP1 regulates the cell cycle mitotic, G1/S, and G2/M phases and Fc fragment of IgE receptor I (FCERI)–mediated NF-κB and MAPK pathway and Fc fragment of IgG receptor (FCGR) activation pathways. Notably, ssGSEA indicated that DNTTIP1 expression was positively correlated with infiltrating levels of Th2 cells, Tfh, NK CD56 bright cells, aDCs, T helper cells, Th1 cells, and macrophages. These findings suggest that DNTTIP1 is correlated with prognosis and immune infiltration in HCC, which lays a foundation for further study of the immune-regulatory role of DNTTIP1 in HCC.

Highlights

  • Hepatocellular carcinoma (HCC) is a serious medical problem that ranks sixth among the most common malignancies and is a third leading cause of cancer-related death (Forner et al, 2018)

  • Wilcoxon rank sum test showed that Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) was significantly correlated with weight (p = 0.047), AFP (p < 0.001), and prothrombin time (p = 0.022)

  • Clinicians have been perplexed for a long time by the early detection of HCC that adopts AFP as an indicator for HCC screening at the early stage

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Summary

Introduction

Hepatocellular carcinoma (HCC) is a serious medical problem that ranks sixth among the most common malignancies and is a third leading cause of cancer-related death (Forner et al, 2018). Over the past 10 years, treatment of HCC has considerably evolved. HCC patients diagnosed at any stage of the disease can benefit from effective treatment that substantially improves their survival. There has been little progress made on the development of clinically useful biomarkers for early detection of HCC over the last 2 decades (Sengupta and Parikh, 2017). The molecular mechanisms underlying tumorigenesis and progression of HCC remain poorly understood (Zhao et al, 2019). There is a critical gap in the current treatment and understanding of HCC due to absence of specific markers for tumor type or disease stage.

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