Analysis of Bulk RNA Sequencing Data Reveals Novel Transcription Factors Associated With Immune Infiltration Among Multiple Cancers
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...
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Published in | Frontiers in immunology Vol. 12; p. 644350 |
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Main Authors | , , , , , , , , , , |
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Language | English |
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20.08.2021
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Abstract | 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. |
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AbstractList | 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. 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. |
Author | Quan, Weili Sun, Luguo Zhao, Qiuchen Cong, Xianling Yi, Jingwen Sun, Hongyan Wang, Qi Zhang, Yi Cheng, Chao Xue, Yaqiang Liu, Lei |
AuthorAffiliation | 1 National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University , Changchun , China 3 College of Life Sciences, Wuhan University , Wuhan , China 4 Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University , Changchun , China 2 Center of Genome Analysis, ABLife BioBigData Institute , Wuhan , China 5 Tissue Bank, China–Japan Union Hospital, Jilin University , Changchun , China |
AuthorAffiliation_xml | – name: 1 National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University , Changchun , China – name: 5 Tissue Bank, China–Japan Union Hospital, Jilin University , Changchun , China – name: 4 Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University , Changchun , China – name: 3 College of Life Sciences, Wuhan University , Wuhan , China – name: 2 Center of Genome Analysis, ABLife BioBigData Institute , Wuhan , China |
Author_xml | – sequence: 1 givenname: Lei surname: Liu fullname: Liu, Lei – sequence: 2 givenname: Qiuchen surname: Zhao fullname: Zhao, Qiuchen – sequence: 3 givenname: Chao surname: Cheng fullname: Cheng, Chao – sequence: 4 givenname: Jingwen surname: Yi fullname: Yi, Jingwen – sequence: 5 givenname: Hongyan surname: Sun fullname: Sun, Hongyan – sequence: 6 givenname: Qi surname: Wang fullname: Wang, Qi – sequence: 7 givenname: Weili surname: Quan fullname: Quan, Weili – sequence: 8 givenname: Yaqiang surname: Xue fullname: Xue, Yaqiang – sequence: 9 givenname: Luguo surname: Sun fullname: Sun, Luguo – sequence: 10 givenname: Xianling surname: Cong fullname: Cong, Xianling – sequence: 11 givenname: Yi surname: Zhang fullname: Zhang, Yi |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Zlatko Trajanoski, Innsbruck Medical University, Austria These authors have contributed equally to this work Reviewed by: Hubert Hackl, Medical University of Innsbruck, Austria; Fatima Sanchez-Cabo, Spanish National Centre for Cardiovascular Research, Spain This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology |
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Title | Analysis of Bulk RNA Sequencing Data Reveals Novel Transcription Factors Associated With Immune Infiltration Among Multiple Cancers |
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