AUTHOR=Luo Na , Sun Xizi , Ma Shengling , Li Xiaoyu , Zhu Wenjun , Fu Min , Yang Feng , Chen Ziqi , Li Qianxia , Zhang Yuanyuan , Peng Xiaohong , Hu Guangyuan 

TITLE=Development of a Novel Prognostic Model of Glioblastoma Based on m6A-Associated Immune Genes and Identification of a New Biomarker

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.868415

DOI=10.3389/fonc.2022.868415

ISSN=2234-943X

ABSTRACT=Background: Accumulating evidence shows that m6A regulates oncogenes and tumor suppressor genes expression, thus playing dual roles in cancer. Likewise, there is a close relationship between the immune system and tumor development and progression. However, for glioblastoma, m6A-associated immunological markers remain to be identified.
Methods: We obtained gene expression, mutation, and clinical data on glioblastoma from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Next, we performed univariate COX-LASSO-multivariate COX regression analyses to establish a prognostic gene signature and develop a corresponding dynamic nomogram application. We then carried out a clustering analysis twice to categorize all samples according to their m6A-regulating and m6A-associated immune genes expression levels (high, medium, and low) and calculated their m6A score. Finally, we performed quantitative reverse transcription-polymerase chain reaction, cell counting kit-8, cell stemness detection, cell migration, and apoptosis detection in vitro assays to determine the biological role of CD81 in glioblastoma cells.
Results: Our glioblastoma risk score model had extremely high prediction efficacy, with the area under the receiver operating characteristic curve reaching 0.9. The web version of the dynamic nomogram application allows rapid and accurate calculation of patients’ survival odds. Survival curves and Sankey diagrams indicated that the high-m6A score group corresponded to the groups expressing medium and low m6A-regulating genes levels and high m6A-associated prognostic immune genes levels. Moreover, these groups displayed lower survival rates and higher immune infiltration. Based on the gene set enrichment analysis, the pathophysiological mechanism may be related to the activation of the immunosuppressive function and related signaling pathways. Besides, the risk score model allowed us to perform immunotherapy benefit assessment. Finally, silencing CD81 in vitro significantly suppressed proliferation, stemness, and migration and facilitated apoptosis in glioblastoma cells.
Conclusion: We developed an accurate and efficient prognostic model. Besides, the correlation analysis of different stratification methods with tumor microenvironment provided a basis for further pathophysiological mechanism exploration. Finally, CD81 may serve as a diagnostic and prognostic biomarker in glioblastoma.