Department of Internal Medicine, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China.
Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Aging (Albany NY). 2020 Oct 22;12(20):20308-20331. doi: 10.18632/aging.103804.
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. 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 expression correlated negatively with immune infiltration. We then explored genes that were co-expressed with in TCGA, and investigated DEGs based on 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.
肿瘤免疫微环境(TIME)是癌症预后和治疗效果的重要决定因素。为了鉴定肺腺癌的免疫相关预后生物标志物,我们使用 ESTIMATE 算法计算了来自癌症基因组图谱(TCGA)的 517 例肺腺癌患者的免疫和基质评分。我们检测了高免疫和基质评分与低免疫和基质评分患者之间的 985 个差异表达基因(DEG),并分析了它们的功能和蛋白质-蛋白质相互作用。在免疫和基质评分较低的肺腺癌患者中上调,与预后不良相关。TISIDB 和 TIMER 数据库表明表达与免疫浸润呈负相关。然后我们探索了在 TCGA 中与共表达的基因,并根据 GSE43580 和 GSE7670 中的表达研究了 DEG。对这些分析的 429 个常见 DEG 进行了功能分析。我们还使用 TCGA 数据进行了基因集富集分析,并使用 UbiBrowser 预测了 TRIM28 的底物。结果表明,TRIM28 可能通过增加 IRF5 和 IRF8 的 SUMO 化来负调控 TIME。在两个肺腺癌细胞系(PC9 和 H1299)中的相关性分析和验证证实了这一发现。因此,TRIM28 可能会使肺腺癌的 TIME 和预后恶化。