UBE2T is a prognostic biomarker and correlated with Th2 cell infiltrates in retinoblastoma

Biochem Biophys Res Commun. 2022 Jul 23:614:138-144. doi: 10.1016/j.bbrc.2022.04.096. Epub 2022 May 6.

Abstract

Objective: This study aimed to screen anaplasia-related genes that influence the progression of retinoblastoma (RB) and to identify immune cells associated with the poor prognosis.

Methods: Differentially expressed genes (DEGs) between retina and RB samples were acquired from gene expression omnibus (GEO) database. Candidate hub genes were screened by taking intersections among the co-expressed genes, the hub nodes, and DEGs of the validation set. The hub genes were identified by receiver operating characteristic (ROC) and quantitative real-time PCR (qPCR). Immune infiltration levels of RB tissues were estimated using single-sample gene set enrichment analysis (ssGSEA). The functions of RB cells were detected by CCK8, EDU and flow cytometry assays.

Results: 665 DEGs involved in the genesis and progression of RB were acquired from GEO database. 29 candidate hub genes were screened by examining 43 co-expressed genes and 63 hub nodes. 9 hub genes (CHEK1, EXO1, FANCI, GTSE1, MELK, MKI67, NCAPH, PRC1, and UBE2T) strongly related to the anaplastic grades were validated by ROC curve analysis (AUC >0.8). Based on the ssGSEA scores, the immune infiltration levels of Th2 cells were positively associated with anaplastic grade. qPCR assay showed that 9 hub genes were upregulated in RB cells, and UBE2T expressed remarkably high. CCK 8, EDU, and flow cytometry assays revealed that UBE2T silencing inhibited the proliferation of RB cells and incited apoptosis.

Conclusions: The increased infiltration of Th2 cells and upregulated expression of 9 hub genes predict a poor prognosis of RB. UBE2T can be a therapeutic target for RB treatment.

Keywords: Anaplasia grade; Immune infiltration; Retinoblastoma; UBE2T.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cell Cycle Proteins / genetics
  • Computational Biology
  • Gene Regulatory Networks
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Nuclear Proteins / genetics
  • Prognosis
  • Protein Serine-Threonine Kinases
  • Retinal Neoplasms*
  • Retinoblastoma* / genetics
  • Th2 Cells / pathology
  • Ubiquitin-Conjugating Enzymes* / metabolism

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • GTSE1 protein, human
  • Microtubule-Associated Proteins
  • NCAPH protein, human
  • Nuclear Proteins
  • UBE2T protein, human
  • Ubiquitin-Conjugating Enzymes
  • MELK protein, human
  • Protein Serine-Threonine Kinases