Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value

Front Immunol. 2024 Jan 11:14:1336187. doi: 10.3389/fimmu.2023.1336187. eCollection 2023.

Abstract

Background: We explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict the prognosis of glioblastoma patients. Aberrant expression of CRYAB is associated with invasive behavior in various tumors, including glioblastoma. However, the specific role and mechanisms of CRYAB in glioblastoma are still unclear.

Methods: We assessed RNA-seq and microarray data from TCGA and GEO databases, combined with scRNA-seq data on glioma patients from GEO. Utilizing the Seurat R package, we identified distinct survival-related gene clusters in the scRNA-seq data. Prognostic pivotal genes were discovered through single-factor Cox analysis, and a prognostic model was established using LASSO and stepwise regression algorithms. Moreover, we investigated the predictive potential of these genes in the immune microenvironment and their applicability in immunotherapy. Finally, in vitro experiments confirmed the functional significance of the high-risk gene CRYAB.

Results: By analyzing the ScRNA-seq data, we identified 28 cell clusters representing seven cell types. After dimensionality reduction and clustering analysis, we obtained four subpopulations within the oligodendrocyte lineage based on their differentiation trajectory. Using CRYAB as a marker gene for the terminal-stage subpopulation, we found that its expression was associated with poor prognosis. In vitro experiments demonstrated that knocking out CRYAB in U87 and LN229 cells reduced cell viability, proliferation, and invasiveness.

Conclusion: The risk model based on CRYAB holds promise in accurately predicting glioblastoma. A comprehensive study of the specific mechanisms of CRYAB in glioblastoma would contribute to understanding its response to immunotherapy. Targeting the CRYAB gene may be beneficial for glioblastoma patients.

Keywords: CRYAB; diagnosis; glioma; immune infiltration; prognosis; tumor immune microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cell Differentiation
  • Glioblastoma* / diagnosis
  • Glioblastoma* / genetics
  • Glioma* / diagnosis
  • Glioma* / genetics
  • Humans
  • Prognosis
  • Tumor Microenvironment / genetics
  • alpha-Crystallin B Chain

Substances

  • CRYAB protein, human
  • alpha-Crystallin B Chain

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Postgraduate Innovation Research and Practice Program of Anhui Medical University [Nos.YJS20230074 and Nos.YJS20230184], Youth Foundation of National Natural Science Foundation of China [Nos. 82003795], Youth Project of Anhui Natural Science Foundation (Nos. 2108085QH330), University Natural Science Research Project of Anhui Province (2023AH053318), Scientific Research Fund, Scientific Research and Cultivation Project of Department of Nursing, and Doctor Research Project of the First Affiliated Hospital of Anhui Medical University [Nos. 2021xkj020, hlpy20210014], Quality Engineering Teaching Research Project of Anhui Medical University[No. 2021xjjyxm12 and 2022zyxwjxalk057], Early contact scientific research training plan for clinical medicine [No. 2021-ZQKY-123], Open Project of Key lab of Dermatology, Ministry of Education, Anhui Medical University[No. AYPYS2022-5]and KFJJ-2020-01.