Clinical Center for Molecular Diagnosis and Therapy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
PLoS One. 2023 Sep 5;18(9):e0291088. doi: 10.1371/journal.pone.0291088. eCollection 2023.
Lung adenocarcinoma is a disease with a high mortality rate, and its mechanism is still unclear. Super-enhancers play an important role in gene expression and also affect the occurrence and development of lung adenocarcinoma, so more and more people pay attention to them. In order to explore the influence of super-enhancer related genes on tumor development, we identified super-enhancer regulated genes related to Epithelial-to-mesenchymal transition (EMT). By analyzing the single-cell sequencing data and the TCGA database of lung adenocarcinoma, we suggest that the up-regulation of TMSB10 in lung adenocarcinoma and its association with poor prognosis may be due to the regulation of super-enhancers during tumor cell metastasis. Using the TCGA lung adenocarcinoma data set, the samples were divided into TMSB10 high-expression group and low-expression group, and it was found that there were significant differences in immune infiltration between the high-expression group and the low-expression group. We parted 513 samples into eight TMSB10-related molecular subtypes using differentially expressed genes of high and low TMSB10 expression groups. We concentrated on four molecular subtypes with the most significant clusters, each with its own characteristics in terms of Immune cell infiltration, prognosis, or pathological stages. In order to predict the four molecular subtypes, we established a prediction model using random forest, and the external test results showed that the prediction accuracy of the model was 0.87. This study may provide potential help for the study of the mechanism of metastasis and invasion of lung adenocarcinoma cells and personalized treatment of lung adenocarcinoma.
肺腺癌是一种死亡率较高的疾病,其发病机制尚不清楚。超级增强子在基因表达中起着重要作用,也影响着肺腺癌的发生和发展,因此越来越多的人开始关注它们。为了探讨超级增强子相关基因对肿瘤发展的影响,我们鉴定了与上皮间质转化(EMT)相关的超级增强子调控基因。通过分析肺腺癌的单细胞测序数据和 TCGA 数据库,我们提出肺腺癌细胞转移过程中超级增强子的调控可能导致 TMSB10 在肺腺癌中的上调及其与不良预后相关。使用 TCGA 肺腺癌数据集,我们将样本分为 TMSB10 高表达组和低表达组,发现高表达组和低表达组之间的免疫浸润存在显著差异。我们使用高表达和低表达 TMSB10 差异表达基因将 513 个样本分为 8 个 TMSB10 相关分子亚型。我们集中研究了四个具有最显著聚类的分子亚型,每个分子亚型在免疫细胞浸润、预后或病理分期方面都有其自身的特点。为了预测这四个分子亚型,我们使用随机森林建立了一个预测模型,外部测试结果表明该模型的预测准确性为 0.87。这项研究可能为研究肺腺癌细胞转移和侵袭的机制以及肺腺癌的个体化治疗提供潜在帮助。