Research Paper Advance Articles

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

Identification of immunity-based molecular subtypes of LUSC patient samples based on the expression of the TOX pathway gene signature. (A) Clustering heat map shows the presence of two clusters among the TCGA-LUSC dataset based on the TOX pathway gene signature. (B) Kaplan–Meier survival curve analysis shows the differences in overall, survival times of cluster 1 and cluster 2 TCGA-LUSC patients. (C) The heatmap shows the expression of DEGs in the cluster 1 and cluster 2 TCGA-LUSC patients. (D) GSEA plot shows the upregulation of genes related to the exhausted CD8+ T cells in the cluster 2 TCGA-LUSC dataset compared to those in the cluster1 TCGA-LUSC dataset. The upregulated genes linked to the exhaustion of CD8+ T cells are shown on the left. Note: NES: normalized enrichment score. (E) Venn diagram shows the numbers of cluster 1 (n=36) and cluster 2 (n=110) molecular subtypes among the high immunity LUSC subgroup (n=146). (F) The histogram plots show the mRNA expression levels of LAPTM5, CSF1R, SLCO2B1 and C1QC in the cluster 1 and cluster 2 LUSC samples. (G) ROC curve analysis shows the sensitivity and accuracy of the 4 hub genes, LAPTM5, CSF1R, SLCO2B1 and C1QC to distinguish cluster 1 and cluster 2 samples based on their expression. The area under the ROC curve (AUC) values demonstrates that all 4 hub genes show high sensitivity and accuracy in distinguishing the LUSC patients belonging to the two clusters. Note: Immunity-High denotes high immunity group; Immunity-Middle denotes medium immunity group; Immunity-Low denotes low immunity group.

Figure 8. Identification of immunity-based molecular subtypes of LUSC patient samples based on the expression of the TOX pathway gene signature. (A) Clustering heat map shows the presence of two clusters among the TCGA-LUSC dataset based on the TOX pathway gene signature. (B) Kaplan–Meier survival curve analysis shows the differences in overall, survival times of cluster 1 and cluster 2 TCGA-LUSC patients. (C) The heatmap shows the expression of DEGs in the cluster 1 and cluster 2 TCGA-LUSC patients. (D) GSEA plot shows the upregulation of genes related to the exhausted CD8+ T cells in the cluster 2 TCGA-LUSC dataset compared to those in the cluster1 TCGA-LUSC dataset. The upregulated genes linked to the exhaustion of CD8+ T cells are shown on the left. Note: NES: normalized enrichment score. (E) Venn diagram shows the numbers of cluster 1 (n=36) and cluster 2 (n=110) molecular subtypes among the high immunity LUSC subgroup (n=146). (F) The histogram plots show the mRNA expression levels of LAPTM5, CSF1R, SLCO2B1 and C1QC in the cluster 1 and cluster 2 LUSC samples. (G) ROC curve analysis shows the sensitivity and accuracy of the 4 hub genes, LAPTM5, CSF1R, SLCO2B1 and C1QC to distinguish cluster 1 and cluster 2 samples based on their expression. The area under the ROC curve (AUC) values demonstrates that all 4 hub genes show high sensitivity and accuracy in distinguishing the LUSC patients belonging to the two clusters. Note: Immunity-High denotes high immunity group; Immunity-Middle denotes medium immunity group; Immunity-Low denotes low immunity group.