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 noncoding 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.

CENP-A is a potential prognostic biomarker and correlated with immune infiltration levels in glioma patients

“…Since the prognostic role of infiltrating immune cells have been proposed across many human cancers ( Gentles et al, 2015 ), we pay attention to the link between glioma immunity and CENP-A in this research. Several research models regarding centromeric factor in cancer proposed the association with immune infiltration ( Shi et al, 2021 ; Zeng et al, 2021 ; Zhou et al, 2021 ). We also showed that CENP-A expression level was associated with the level of infiltrating immune cells in gliomas and presented the strongest correlation with Th2 cells and pDCs.…”

CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma

“…It was worth noting that the function of highly expressed CENPE was also enriched in the T cell receptor signaling pathway. It had been reported that high expression of CENPE promoted immune cell infiltration, especially B cells [ 63 ]. Similarly, we also found that CENPE was significantly and positively related to CD8 + T cell and macrophage.…”

Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario

“…Regarding pediatric tumors, this kinase is associated with lower overall survival and EFS rates in EPN [ 344 , 345 ], RMS [ 346 , 347 ] and NB [ 348 ]. In silico analyses have also demonstrated that CDK1 is differentially expressed in RB [ 349 ] and plays a key role in the development of OS, since its negative regulation or depletion leads to significant decreases in proliferation while inducing apoptosis [ 350 , 351 , 352 , 353 ].…”