Analysis of Bulk RNA Sequencing Data Reveals Novel Transcription Factors Associated With Immune Infiltration Among Multiple Cancers

• Main Authors: Lei Liu, Qiuchen Zhao, Chao Cheng, Jingwen Yi, Hongyan Sun, Qi Wang, Weili Quan, Yaqiang Xue, Luguo Sun, Xianling Cong, Yi Zhang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-08-01
• Series: Frontiers in Immunology
• Subjects: immune infiltration; pan-cancers; transcription factor; immune cell types; FOXM1; MYBL2
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2021.644350/full

Tumor-infiltrating immune cells shape the tumor microenvironment and are closely related to clinical outcomes. Several transcription factors (TFs) have also been reported to regulate the antitumor activity and immune cell infiltration. This study aimed to quantify the populations of different immune cells infiltrated in tumor samples based on the bulk RNA sequencing data obtained from 50 cancer patients using the CIBERSORT and the EPIC algorithm. Weighted gene coexpression network analysis (WGCNA) identified eigengene modules strongly associated with tumorigenesis and the activation of CD4+ memory T cells, dendritic cells, and macrophages. TF genes FOXM1, MYBL2, TAL1, and ERG are central in the subnetworks of the eigengene modules associated with immune-related genes. The analysis of The Cancer Genome Atlas (TCGA) cancer data confirmed these findings and further showed that the expression of these potential TF genes regulating immune infiltration, and the immune-related genes that they regulated, was associated with the survival of patients within multiple cancers. Exome-seq was performed on 24 paired samples that also had RNA-seq data. The expression quantitative trait loci (eQTL) analysis showed that mutations were significantly more frequent in the regions flanking the TF genes compared with those of non-TF genes, suggesting a driver role of these TF genes regulating immune infiltration. Taken together, this study presented a practical method for identifying genes that regulate immune infiltration. These genes could be potential biomarkers for cancer prognosis and possible therapeutic targets.