Research Paper Volume 13, Issue 3 pp 3819—3842

Four hub genes regulate tumor infiltration by immune cells, antitumor immunity in the tumor microenvironment, and survival outcomes in lung squamous cell carcinoma patients

Tuo Zhang1, , Haitang Yang1, , Beibei Sun2, , Feng Yao1, ,

  • 1 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
  • 2 Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

Received: May 19, 2020       Accepted: October 2, 2020       Published: January 10, 2021
How to Cite

Copyright: © 2021 Zhang 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.


In this study, we performed bioinformatics analyses to identify hub genes that regulate tumor infiltration by immune cells and antitumor immunity in the lung squamous cell carcinoma (LUSC). We identified 1738 robust and stable differentially expressed genes (DEGs) in the LUSC tissues based on robust rank aggregation (RRA) analysis of RNA-sequencing data from 5 GEO-LUSC datasets. We then classified TCGA-LUSC patients based on ssGSEA and ESTIMATE analyses of LUSC tissues into high, medium and low immunity subgroups showing significant differences in tumor purity. Weighted gene co-expression network analysis of the robust DEGs revealed five immunity-related modules, including the brown module with 762 DEGs and 30 hub genes showing the highest correlation with the immunity-related LUSC patient subgroups and their clinicopathological characteristics. We selected four hub genes, LAPTM5, C1QC, CSF1R and SLCO2B1, for validation of the immunity status and prognosis of LUSC patients. High expression of these four genes correlated with increased infiltration of immune cell types, upregulation of the immunosuppressive TOX pathway genes, CD8+ T cell exhaustion, and shorter overall survival of LUSC patients. These findings demonstrate that four hub genes regulate tumor infiltration of immune cells, anti-tumor immunity, and survival outcomes in LUSC patients.


GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; WGCNA: Weighted Gene Co-expression Network Analysis; GS: gene significance; MM: module membership; TNM: Tumor Node Metastasis; GSEA: Gene Set Enrichment Analysis; GSVA: Gene Set Variation Analysis; ssGSEA: single sample gene set enrichment analysis; TCGA-LUSC dataset: The Cancer Genome Atlas Lung Squamous cell Carcinoma Dataset; ROC: receiver operating characteristic; AUC: area under the ROC curve; DEG: differentially expressed gene; RRA: robust rank aggregation.