RRC ID 76383
Author Liu J, Han X, Chen L, Han D, Mu X, Hu X, Wu H, Wu H, Liu W, Zhao Y.
Title TRIM28 is a distinct prognostic biomarker that worsens the tumor immune microenvironment in lung adenocarcinoma.
Journal Aging (Albany NY)
Abstract The tumor immune microenvironment (TIME) is an important determinant of cancer prognosis and treatment efficacy. To identify immune-related prognostic biomarkers of lung adenocarcinoma, we used the ESTIMATE algorithm to calculate the immune and stromal scores of 517 lung adenocarcinoma patients from The Cancer Genome Atlas (TCGA). We detected 985 differentially expressed genes (DEGs) between patients with high and low immune and stromal scores, and we analyzed their functions and protein-protein interactions. TRIM28 was upregulated in lung adenocarcinoma patients with low immune and stromal scores, and was associated with a poor prognosis. The TISIDB and TIMER databases indicated that TRIM28 expression correlated negatively with immune infiltration. We then explored genes that were co-expressed with TRIM28 in TCGA, and investigated DEGs based on TRIM28 expression in GSE43580 and GSE7670. The 429 common DEGs from these analyses were functionally analyzed. We also performed a Gene Set Enrichment Analysis using TCGA data, and predicted substrates of TRIM28 using UbiBrowser. The results indicated that TRIM28 may negatively regulate the TIME by increasing the SUMOylation of IRF5 and IRF8. Correlation analyses and validations in two lung adenocarcinoma cell lines (PC9 and H1299) confirmed these findings. Thus, TRIM28 may worsen the TIME and prognosis of lung adenocarcinoma.
Volume 12(20)
Pages 20308-20331
Published 2020-10-22
DOI 10.18632/aging.103804
PII 103804
PMID 33091876
PMC PMC7655206
MeSH Adenocarcinoma of Lung / genetics Adenocarcinoma of Lung / immunology Adenocarcinoma of Lung / metabolism* Adenocarcinoma of Lung / therapy Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Line, Tumor Disease-Free Survival Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Regulatory Networks Humans Interferon Regulatory Factors / metabolism Lung Neoplasms / genetics Lung Neoplasms / immunology Lung Neoplasms / metabolism* Lung Neoplasms / therapy Male Protein Interaction Maps Risk Assessment Risk Factors Signal Transduction Sumoylation Transcriptome Tripartite Motif-Containing Protein 28 / genetics Tripartite Motif-Containing Protein 28 / metabolism* Tumor Microenvironment*
IF 4.831
Human and Animal Cells PC-9(RCB4455)