The molecular feature of macrophages in tumor immune microenvironment of glioma patients

Hao Zhang1, Yue-Bei Luo2, Wantao Wu3

  • 1Department of Neurosurgery, Xiangya Hospital, Central South University, China.

Abstract

Insights

Macrophages, particularly M2 macrophages, significantly influence glioma progression. A novel MScore model accurately predicts worse patient survival, highlighting macrophages as key therapeutic targets in brain tumors.

Area of Science:

  • Neuro-oncology
  • Immunology
  • Computational Biology

Background:

  • Gliomas are common primary central nervous system tumors.
  • Macrophages play a crucial role in tumor growth and progression.

Purpose of the Study:

  • To identify macrophage-related genes in glioma.
  • To develop a prognostic model (MScore) for glioma patients based on macrophage activity.

Main Methods:

  • Weighted gene co-expression network analysis.
  • Machine learning (Pamr, SVM, neural network) for clustering.
  • Elastic regression, principal component analysis (PCA) for DEGs and MScore construction.
  • Single-cell sequencing for evaluating macrophage gene expression.
  • Validation on 15 glioma and 5842 pan-cancer datasets.

Main Results:

  • Macrophages negatively correlate with glioma patient survival.
  • Twenty-six macrophage-specific DEGs were identified and highly expressed in tumor-associated macrophages.
  • The MScore model accurately stratified patient survival, predicting worse outcomes.
  • MScore demonstrated prognostic value in external validation cohorts and confirmed by immunohistochemistry.

Conclusions:

  • Macrophages, especially M2 subtypes, modulate glioma progression.
  • The MScore serves as a robust prognostic biomarker for glioma.
  • Further experimental studies are warranted to explore macrophage-targeted therapies.
Keywords:
ACC, Adrenocortical carcinomaBBB, brain blood barrierBLCA, Bladder Urothelial CarcinomaBRCA, Breast invasive carcinomaCDF, cumulative distribution functionCESC, Cervical squamous cell carcinoma and endocervical adenocarcinomaCGGA, Chinese Glioma Genome AtlasCHOL, CholangiocarcinomaCNA, copy number alternationsCNV, copy number variationCOAD, Colon adenocarcinomaCSF-1, colony-stimulating factor-1DLBC, Lymphoid Neoplasm Diffuse Large B-cell LymphomaDMP, differentially methylated positionESCA, Esophageal carcinomaGBM, glioblastomaGEO, Gene Expression OmnibusGO, gene ontologyGSEA, gene set enrichment analysisGSVA, gene set variation analysisGlioma microenvironmentHNSC, Head and Neck squamous cell carcinomaIGR, intergenic regionIHC, immunohistochemistryIL, interleukinImmunotherapyKEGG, Kyoto Encyclopaedia of Genes and GenomesKICH, Kidney ChromophobeKIRC, Kidney renal clear cell carcinomaKIRP, Kidney renal papillary cell carcinomaLGG, low grade gliomaLIHC, Liver hepatocellular carcinomaLUAD, Lung adenocarcinomaLUSC, Lung squamous cell carcinomaMMP-2, matrix metalloproteinase-2MT1, MMP membrane type 1 matrix metalloproteaseMachine learningMacrophageOV, Ovarian serous cystadenocarcinomaPAAD, Pancreatic adenocarcinomaPAM, partition around medoidsPCA, principal component analysisPCPG, Pheochromocytoma and ParagangliomaPRAD, Prostate adenocarcinomaPrognostic modelREAD, Rectum adenocarcinomaSARC, SarcomaSKCM, Skin Cutaneous MelanomaSNP, single-nucleotide polymorphismSNV, single-nucleotide variantSTAD, Stomach adenocarcinomaSVM, Support Vector MachinesTAM, tumor associated macrophageTCGA, The Cancer Genome AtlasTGF-β, tumor growth factor-βTHCA, Thyroid carcinomaTHYM, ThymomaTIMP-2, tissue inhibitor of metalloproteinase-2TLR2, toll-like receptor 2TME, tumor microenvironmentTNFα, tumor necrosis factor αTSS, transcription start siteUCEC, Uterine Corpus Endometrial CarcinomaUCS, Uterine CarcinosarcomaWGCNA, weighted gene co-expression network analysispamr, prediction analysis for microarrays