AUTHOR=Liu Lei , Zhao Qiuchen , Cheng Chao , Yi Jingwen , Sun Hongyan , Wang Qi , Quan Weili , Xue Yaqiang , Sun Luguo , Cong Xianling , Zhang Yi 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.644350

DOI=10.3389/fimmu.2021.644350

ISSN=1664-3224

ABSTRACT=Tumor-infiltrating immune cells shape tumor microenvironment and are closely linked to immunotherapy. Several transcription factors (TFs) have been reported to regulate the anti-tumor activity, and also the immune cell infiltration and activity. Here we applied the CIBERSORT algorithm to quantify the populations of different immune cells infiltrated in the tumor samples based on the bulk RNA sequencing data obtained from 50 cancer patients. WGCNA analysis 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 sub-networks of the eigengene modules which associated with immune related genes. Analysis of TCGA cancer data confirmed these findings and further showed that the expression of these potential immune-infiltration regulatory TF genes and the immune-related genes they regulate is associated with the survival of patients within multiple cancers. Exosome-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 than the non-TF genes, suggesting a driver role of these immune-infiltration regulatory TFs. Taken together, this study presents a practical method for identifying genes regulating immune infiltration; these genes could be potential biomarkers for cancer prognosis and possible therapeutic targets.