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
|
Resource |
Human and Animal Cells |
PC-9(RCB4455) |