HOXD9 is a potential prognostic biomarker involved in immune microenvironment of glioma

J Cancer Res Clin Oncol. 2023 Nov;149(16):14911-14926. doi: 10.1007/s00432-023-05275-z. Epub 2023 Aug 21.

Abstract

Background: Glioma is the prevailing malignant tumor affecting the brain and central nervous system, constituting over 80% of all malignant brain tumors. HOXD9 has been implicated in the development of glioma, but the specific mechanism of its influence on glioma pathogenesis remains incompletely understood. The purpose of this study was to investigate the role of HOXD9 in glioma and examine the changes in HOXD9 expression during the progression of glioma, thus contributing new insights into the pathogenesis of glioma.

Methods: Glioma samples from the Cancer Gene Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets were included in this study. Variations in HOXD9 expression in gliomas between different subgroups of multiple clinical characteristics were explored, and the expression was validated in glioma samples using qRT-PCR and western blotting. Next, the impact of HOXD9 on the prognosis of gliomas was explored by survival analysis, receiver operating characteristic curve, and nomogram plots. Subsequently, the association between HOXD9 and the tumor immune microenvironment was explored using the ssGSEA algorithm and the ESTIMATE algorithm. Then, immune-related pathways associated with HOXD9 were determined by differential express analysis and GSEA. Finally, HOXD9-related genomic alterations were identified.

Results: HOXD9 expression is upregulated and correlated with malignant properties in glioma. Similarly, our validation results showed significantly upregulated protein and mRNA levels of HOXD9 in glioma brain tissues. In addition, high HOXD9 expression was indicative of a poor prognosis for glioma patients. Additionally, elevated HOXD9 levels were associated with reduced tumor purity and higher levels of immune invasion. Finally, HOXD9 was significantly associated with genomic alterations.

Conclusion: Overall, this study has unveiled a significant association between HOXD9 and the prognosis and survival of glioma patients. Our findings highlight the potential of HOXD9 as a prognostic biomarker, implicating its role in influencing the glioma immune microenvironment.

Keywords: Bioinformatics; Biomarker; Glioma; HOXD9; Immune microenvironment.

MeSH terms

  • Biomarkers
  • Brain Neoplasms* / genetics
  • Glioma* / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Neoplasm Proteins
  • Oncogenes
  • Prognosis
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers
  • HOXD9 protein, human
  • Neoplasm Proteins
  • Homeodomain Proteins