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. 2024 Sep 10;15(1):423.
doi: 10.1007/s12672-024-01295-4.

Expression and biological significance of topoisomerase II α (TOP2A) in oral squamous cell carcinoma

Xujie Cheng  1 , Yuxing Wei  1 , Limei Deng  1 , Hao Dong  1 , Huiping Wei  1 , Cheng Xie  1 , Yangjuan Tuo  1 , Meiyu Chen  1 , Hao Qin  1 , Yong Cao  2
Affiliations

Expression and biological significance of topoisomerase II α (TOP2A) in oral squamous cell carcinoma

Xujie Cheng et al. Discov Oncol. .

Abstract

Background: Topoisomerase II α(TOP2A) is usually highly expressed in rapidly proliferating cells, and its expression is regulated by cell cycle. The relationship between TOP2A and oral squamous cell carcinoma (OSCC) needs further study.

Methods: TOP2A immunoreactivity was analyzed using immunohistochemical (IHC) staining analysis in specimens from 20 OSCC patients. Based on the high-throughput sequencing and gene microarray database, the expression of TOP2A mRNA in OSCC was calculated and its ability to identify OSCC tissues was evaluated by diagnostic analysis. CRISPR screen was used to select the genes necessary for OSCC cell growth, and the gene set was analyzed for function enrichment. Single-cell RNA sequencing analysis was conducted to evaluate the expression level of TOP2A mRNA in OSCC cells.

Results: Compared with normal oral tissues, the expression of TOP2A protein was up-regulated in OSCC tissues. A total of 1240 OSCC and 428 non-OSCC oral tissue samples were included based on high-throughput dataset retrieval, and it was confirmed that TOP2A mRNA was highly expressed in OSCC tissues [SMD = 1.51 (95% CI 0.94-2.07), sROC AUC = 0.96 (95% CI 0.94-0.98)]. As an essential gene for OSCC cell growth, single-cell RNA sequencing data also confirmed that TOP2A mRNA expression was up-regulated in OSCC cells.

Conclusion: The up-regulation of TOP2A may play a pivotal role in OSCC.

Keywords: Biomarkers; CRISPR-screen; Expression differences; Oral squamous cell carcinoma; Single-cell RNA sequencing; TOP2A.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Expression level of TOP2A protein in normal oral and OSCC tissues. a, b Immunochemistry of squamous cell carcinoma tissue. c, d Immunochemistry of adjacent oral tissue immunochemistry
Fig. 2
Fig. 2
Expression levels of TOP2A in OSCC tissues and normal tissues. a Comparison of TOP2A mRNA expression levels in the two groups of samples; b comprehensive assessment of TOP2A mRNA expression levels in OSCC tissues; c publication bias test of the included datasets
Fig. 3
Fig. 3
Potential clinical significance of high expression of TOP2A in OSCC tissues. a Forest plot of sensitivity and specificity; b Summary receiver operating characteristic curve plot; c Fogan plot showing the positive and negative likelihood ratios of TOP2A mRNA highly expressed in OSCC tissues
Fig. 4
Fig. 4
Biological pathways involved in genes essential for oral squamous cell carcinoma cell growth
Fig. 5
Fig. 5
Expression of TOP2A at the level of oral squamous cell carcinoma cells. a Eigengenes of PC1 and PC2; b t-distributed random neighbor embedding (t-SNE) distribution of 16 cell clusters by unsupervised clustering; c Eigengenes of 16 cell subsets; d TOP2A expression distribution in 8 types of cells
Fig. 6
Fig. 6
Analysis of oral squamous cell carcinoma cells developmental trajectories. a The developmental process of oral squamous cell carcinoma cells defined according to the expression patterns of motif-characterized genes; b the distribution of different oral squamous cell carcinoma cells subsets in the developmental trajectory of oral squamous cell carcinoma cells; c the chronological score of oral squamous cell carcinoma cells differentiation calculated according to the developmental trajectory of oral squamous cell carcinoma cells; d pseudo-temporal differential gene heatmap (number of clusters = number of cell states = 5); e TOP2A expression distribution along the trajectory of oral squamous cell carcinoma cells; f dynamic changes of TOP2A expression levels in different cell states during OSCC cell differentiation
See this image and copyright information in PMC

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