mRNA-seq-based analysis predicts: AEG-1 is a therapeutic target and immunotherapy biomarker for pan-cancer, including OSCC

Front Immunol. 2024 Oct 17:15:1484226. doi: 10.3389/fimmu.2024.1484226. eCollection 2024.

Abstract

Background: The aberrant expression of AEG-1 is significantly correlated with tumorigenesis, development, neurodegeneration and inflammation. However, the relationship between AEG-1 expression and immune infiltration in OSCC, as well as other tumor types, has yet to be comprehensively analyzed.

Methods: The expression levels, prognostic and clinicopathological characteristics, mutation patterns and methylation landscapes of AEG-1 in various tumors were obtained from multiple databases, including TIMER, GEPIA, HPA, TCGA, UALCAN, cBioPortal, SMART and TISIDB, in addition to single-cell RNA-seq data. The integration of these datasets facilitated the elucidation of the relationships among pan-cancer cellular heterogeneity, immune infiltration and AEG-1 expression levels. In vitro experiments created AEG-1 overexpressing cell lines, and mRNA-seq analyzed AEG-1-related differential genes in OSCC. RT-PCR validated these findings in vivo using xenograft tumors. Tumor cell lines were developed to study AEG-1's effects through H&E, Masson, and PAS staining. Immunohistochemistry examined AEG-1-related gene expression patterns.

Results: Our analysis demonstrated that AEG-1 is highly expressed across various cancer types and is associated with tumor grade and patient prognosis. Additionally, AEG-1 amplification was observed in multiple cancers. Notably, we identified a significant elevation of AEG-1 expression in OSCC, which strongly correlated with patient prognosis and immune infiltration. Through mRNA-seq analysis of differentially expressed genes and immune-related gene sets, we identified a strong correlation between AEG-1 and immune infiltration markers such as LCP2, CD247, HLA-DPA1, HLA-DRA, HLA-DRB1, CIITA and CD74 in OSCC. Additionally, AEG-1 was found to regulate Th1/Th2 immune homeostasis, promote glycogen accumulation, and contribute to tumor fibrosis.

Conclusion: In conclusion, AEG-1 significantly correlates with prognosis and immune infiltration across various cancer types and holds potential as a novel prognostic immune biomarker for OSCC. This finding may facilitate the identification of patients who are most likely to benefit from adjuvant immunotherapy.

Keywords: AEG-1; OSCC; immune infiltration; mRNA-seq; pan-cancer.

MeSH terms

  • Animals
  • Biomarkers, Tumor* / genetics
  • Cell Adhesion Molecules* / genetics
  • Cell Adhesion Molecules* / metabolism
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunotherapy / methods
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Mice, Nude
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / immunology
  • Mouth Neoplasms / therapy
  • Prognosis
  • RNA, Messenger / genetics
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • RNA-Seq
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology
  • Xenograft Model Antitumor Assays

Substances

  • MTDH protein, human
  • RNA-Binding Proteins
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • Membrane Proteins
  • RNA, Messenger

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the Central Support for the Reform and Development of Local Universities Project investigated the influence and mechanism of PLP1 point mutation on the occurrence of neurological diseases. Funding for the Reserve Leader of Provincial Leading Talent Echelon (0401-21992139923).