Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma

ABSTRACT

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub genes, including benzimidazoles 1 (BUB1), cyclin dependent kinase 1 (CDK1), centromere protein E (CENPE), kinesin family member 20A (KIF20A), PDZ binding kinase (PBK), and targeting protein for xklp2 (TPX2). Drug sensitivity analysis showed that nelarabine was positively correlated with five hub genes. All six genes were expressed differently in six immune subtypes and were positively correlated with stemness indices in most human cancer types. Since CENPE is the least known hub gene in retinoblastoma, we further analyzed the potential non-coding RNAs and transcription factors that regulate CENPE and built interaction networks of competing endogenous RNA and transcription factors. Immune cell infiltration, especially by plasma and B cells, was enhanced in samples with high CENPE expression. Pan-cancer analysis illustrated that CENPE was highly expressed in a wide range of human tumors. In vitro validation revealed that CENPE was significantly upregulated at both the mRNA and protein levels in retinoblastoma cells. In conclusion, CENPE, along with other hub genes, could serve as a potential biomarker and intervention target for retinoblastoma.

KEYWORDS:

• Retinoblastoma
• centromere protein E (CENPE)
• biomarker
• Gene Expression Omnibus (GEO)
• bioinformatics
• RT-qPCR
• immunoblotting

Research highlights

1. CENPE, BUB1, CDK1, KIF20A, PBK, and TPX2 are potential biomarkers of retinoblastoma.

2. CENPE expression is positively related with immune cell infiltration.

3. CENPE and the five other hub genes are highly expressed in various other cancers.

4. Nelarabine may be a potential antitumor agent in the treatment of retinoblastoma.

Acknowledgements

The authors thank “Taylor & Francis Editing Services” for language editorial assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets (GSE24673, GSE97508, and GSE110811) analyzed for this study can be found in the Gene Expression Omnibus (GEO) database [https://www.ncbi.nlm.nih.gov/geo/].

Author contributions

Ke Shi performed bioinformatic analysis and wrote the manuscript. Xinyue Zhu conducted in vitro experiments and statistical analysis. Jingfa Zhang, Jiali Wu and Yuhong Chen revised the manuscript for important content. Xiaodong Sun designed of the study and revised the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the [National Key R&D Program] under Grant [2017YFA0105301]; the [National Natural Science Foundation of China] under Grant [81730026, 81760176, and 81960158]; the [Science and Technology Commission of Shanghai Municipality] under Grant [20Z11900400]; the [Shanghai Hospital Development Center] under Grant [SHDC2020CR2040B]; the [Cultivation Program of National Natural Science Foundation for Outstanding Youth] under Grant [20202ZDB01014]; and the [Key Program of Youth Science Foundation of Jiangxi Province] under Grant [20202ACBL216009].