<i>TRIM28</i> is a distinct prognostic biomarker that worsens the tumor immune microenvironment in lung adenocarcinoma

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.

TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion

“…Detected in cell nuclei but not in cytoplasm, TRIM28 serves as an important factor in the posttranslational mechanism to regulate various cell functions, such as transcriptional regulation of p53 suppression by promoting its ubiquitination and degradation [ 44 , 45 ]. In addition, TRIM28 has an important role in the oncogenesis in different cancer types [ 46 , 47 ]. TRIM28 expression is elevated in a variety of tumours, including breast cancer, gastric cancer and lung cancer [ 46 , 47 , 48 , 49 ].…”

“…In addition, TRIM28 has an important role in the oncogenesis in different cancer types [ 46 , 47 ]. TRIM28 expression is elevated in a variety of tumours, including breast cancer, gastric cancer and lung cancer [ 46 , 47 , 48 , 49 ]. In a clinical study of patients with early-stage lung tumour, TRIM28 expression significantly correlated with overall survival [ 48 ].…”

“…RT-qPCR was performed with FAM-MGB probes with Fluidigm BioMark HD System RT-PCR (Fluidigm Corporation, San Francisco, CA, USA) using 48.48 Dynamic Arrays IFC [ 63 ], where 42 samples and 24 assays (probes) were mixed pairwise in nanolitre chambers to enable parallel analysis of 2304 reactions. Visualization and analysis of qPCR results were done using the Fluidigm RT-qPCR analysis software and quantGenius software [ 47 ]. Relative copy numbers of mRNA were normalized to housekeeping genes HPRT1 and GAPDH .…”

High TNFSF13B expression as a predictor of poor prognosis in adrenocortical carcinoma

“…UbiBrowser (http://ubibrowser.ncpsb.org/) is an integrated bioinformatics website tool designed to help users explore the predicted and reported E3 substrate interactions and ubiquitination sites of substrate proteins by querying E3 or substrate; it contains 1,295 reported E3-substrate interactions and 8,255 predicted E3-substrate interactions (27). In the network view, the central node is the substrate to be queried, and the surrounding nodes are the predicted E3 ligases.…”

“…STRING (version 11.0, http://string-db.org) is a database of known and predicted PPI networks (27). We used this tool to construct a PPI network and predict potential interactions between TNFSF13B and its targets.…”