Identification of Novel Characteristics in TP53-Mutant Hepatocellular Carcinoma Using Bioinformatics
Open Access
- 16 May 2022
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Genetics
- Vol. 13, 874805
- https://doi.org/10.3389/fgene.2022.874805
Abstract
Background: TP53 mutations are the most frequent mutations in hepatocellular carcinoma (HCC) and affect the occurrence and development of this cancer type. Therefore, it is essential to clarify the function and mechanism of TP53 mutations in HCC. Methods: We performed a sequence of bioinformatic analyses to elucidate the characteristics of TP53 mutations in HCC. We downloaded the data of hepatocellular carcinoma from The Cancer Genome Atlas database and used different R packages for serial analyses, including gene mutation analysis, copy number variation analysis, analysis of the tumor mutational burden and microsatellite instability, differential gene expression analysis, and functional enrichment analysis of TP53 mutations, and performed gene set enrichment analysis. We established a protein-protein interaction network using the STRING online database and used the Cytoscape software for network visualization, and hub gene screening. In addition, we performed anticancer drug sensitivity analysis using data from the Genomics of Drug Sensitivity in Cancer. Immune infiltration and prognosis analyses were also performed. Results: Missense mutations accounted for a great proportion of HCC mutations, the frequency of single nucleotide polymorphisms was high, and C > T was the most common form of single nucleotide variations. TP53 had a mutation rate of 30% and was the most commonly mutated gene in HCC. In the TP53 mutant group, the tumor mutational burden (p < 0.001), drug sensitivity (p < 0.05), ESTIMATE score (p = 0.038), and stromal score (p < 0.001) dramatically decreased. The Cytoscape software screened ten hub genes, including CT45A1, XAGE1B, CT55, GAGE2A, PASD1, MAGEA4, CTAG2, MAGEA10, MAGEC1, and SAGE1. The prognostic model showed a poor prognosis in the TP53 mutation group compared with that in the wild-type group (overall survival, p = 0.023). Univariate and multivariate cox regression analyses revealed that TP53 mutation was an independent risk factor for the prognosis of HCC patients (p Conclusion: This study further deepened our understanding of TP53-mutated HCC, provided new insights into a precise individualized therapy for HCC, and has particular significance for prognosis prediction.This publication has 52 references indexed in Scilit:
- clusterProfiler: an R Package for Comparing Biological Themes Among Gene ClustersOMICS: A Journal of Integrative Biology, 2012
- Hepatocellular Carcinoma: Novel Molecular Approaches for Diagnosis, Prognosis, and TherapyAnnual Review of Medicine, 2010
- When mutants gain new powers: news from the mutant p53 fieldNature Reviews Cancer, 2009
- Inhibitory B7-family molecules in the tumour microenvironmentNature Reviews Immunology, 2008
- GenePattern 2.0Nature Genetics, 2006
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction NetworksGenome Research, 2003
- Cancer immunoediting: from immunosurveillance to tumor escapeNature Immunology, 2002
- The humoral immune response to p53 in patients with hepatocellular carcinoma is specific for malignancy and independent of the α-fetoprotein status,Journal of Hepatology, 1993
- Chromosome 17 Deletions and p53 Gene Mutations in Colorectal CarcinomasScience, 1989