Identification of Novel Characteristics in TP53-Mutant Hepatocellular Carcinoma Using Bioinformatics

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 <0.05). The constructed prognostic model had a favorable forecast value for the prognosis of HCC patients at 1 and 3 years (1-year AUC = 0.752, 3-years AUC = 0.702).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.

LOCC: a novel visualization and scoring of cutoffs for continuous variables

“…We also ranked TP53 expression from low to high so the LOCC graph will show a significant HR above 1, reducing overlapping lines and making it easier to read the graph (Fig 3D). Therefore, both expression and mutation of TP53 can be used in combination to help determine the prognosis of patients with LIHC, which is in line with previous studies (16,17).…”

Prognosis and personalized medicine prediction by integrated whole exome and transcriptome sequencing of hepatocellular carcinoma

“… Zhang et al (2021) found two directly regulated lncRNA associated with TP53 mutations in HCC. These studies provide new insights into personalized prediction methods, but the average frequency of TP53 mutations in HCC is about 30% ( Yang et al, 2022 ). The prognostic model for patients with TP53 wild-type HCC is not clear.…”

Bioinformatic analysis the expression and clinical significance of CDRT15 in cholangiocarcinoma using TCGA database

“…In PubMed and other databases, we found that there was a lack of CDRT15 studies. [25,26] We analyzed the correlation between expression levels of CDRT15 and 24 types of immune cell infiltration in CCA, and the result showed that the CDRT15 expression was negatively correlated with the Treg, DCs, and Cytotoxic cells. We considered that CDRT15 may be involved in the immune infiltration process of CCA and play a certain role.…”