Research Paper Volume 13, Issue 4 pp 5718—5747

Comprehensive analysis of macrophage-related multigene signature in the tumor microenvironment of head and neck squamous cancer

Bo Lin1,2,3, , Hao Li4, , Tianwen Zhang1,2, , Xin Ye2, , Hongyu Yang1,2,3, , Yuehong Shen1,2,3, ,

  • 1 Stomatological Center, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
  • 2 Guangdong Provincial High-level Clinical Key Specialty, Shenzhen, Guangdong, China
  • 3 Guangdong Province Engineering Research Center of Oral Disease Diagnosis and Treatment, Shenzhen, Guangdong, China
  • 4 Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China

Received: March 9, 2020       Accepted: December 16, 2020       Published: February 11, 2021      

https://doi.org/10.18632/aging.202499
How to Cite

Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Macrophages are among the most abundant cells of the tumor microenvironment in head and neck squamous cancer (HNSC). Although the marker gene sets of macrophages have been found, the mechanism by which they affect macrophages and whether they further predict the clinical outcome is unclear. In this study, a univariate COX analysis and a random forest algorithm were used to construct a prognostic model. Differential expression of the key gene, methylation status, function, and signaling pathways were further analyzed. We cross-analyzed multiple databases to detect the relationship between the most critical gene and the infiltration of multiple immune cells, as well as its impact on the prognosis of pan-cancer. FANCE is recognized as hub gene by different algorithms. It was overexpressed in HNSC, and high expression was predictive of better prognosis. It might promote apoptosis through the Wnt/β-catenin pathway. The expression of FANCE is inversely proportional to the infiltration of CD4 + T cells and their subsets, tumor-associated macrophages (TAMs), M2 macrophages, but positively co-expressed with M1 macrophages. In summary, FANCE was identified as the hub gene from the macrophage marker gene set, and it may improve the prognosis of HNSC patients by inhibiting lymphocytes and tumor-associated macrophages infiltration.

Abbreviations

TCGA: The Cancer Genome Atlas; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; TAM: Tumor-Associated Macrophage; PPI: Protein-Protein Interaction; ROC: Receiver Operating characteristic Curve; AUC: Area Under the Curve; STRING: Search Tool for the Retrieval of Interacting Genes/Proteins; GSEA: Gene Set Enrichment Analysis; ssGSEA: single sample of GSEA; GSVA: Gene Set Variation Analysis; TIMER: Tumor IMmune Estimation Resource; ESTIMATE: Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data; FA: Fanconi Anemia.