Research Paper Volume 12, Issue 20 pp 20308—20331
TRIM28 is a distinct prognostic biomarker that worsens the tumor immune microenvironment in lung adenocarcinoma
- 1 Department of Internal Medicine, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China
- 2 Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- 3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Received: April 20, 2020 Accepted: July 9, 2020 Published: October 22, 2020
https://doi.org/10.18632/aging.103804How to Cite
Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
ACC: adrenocortical carcinoma; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CI: confidence interval; DEGs: differentially expressed genes; DFS: disease-free survival; DMFS: distant metastasis-free survival; DSS: disease-specific survival; FP: first progression; HR: hazard ratio; KIRP: kidney renal papillary cell carcinoma; LGG: brain lower-grade glioma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; MESO: mesothelioma; NSCLC: non-small-cell lung cancer; OS: overall survival; PD1: programmed cell death-1; PD-L1: programmed cell death ligand-1; PPI: protein-protein interaction; RFS: recurrence-free survival; SKCM: skin cutaneous melanoma; TCGA: The Cancer Genome Atlas; TIME: tumor immune microenvironment; TRIM: Tripartite motif-containing.