Table2_Single-Cell RNA-Seq Reveals the Promoting Role of Ferroptosis Tendency During Lung Adenocarcinoma EMT Progression.XLSX

Epithelial-mesenchymal transition (EMT) and ferroptosis are two important processes in biology. In tumor cells, they are intimately linked. We used single-cell RNA sequencing to investigate the regulatory connection between EMT and ferroptosis tendency in LUAD epithelial cells. We used Seurat to construct the expression matrix using the GEO dataset GSE131907 and extract epithelial cells. We found a positive correlation between the trends of EMT and ferroptosis tendency. Then we used SCENIC to analyze differentially activated transcription factors and constructed a molecular regulatory directed network by causal inference. Some ferroptosis markers (GPX4, SCP2, CAV1) were found to have strong regulatory effects on EMT. Cell communication networks were constructed by iTALK and implied that Ferro_High_EMT_High cells have a higher expression of SDC1, SDC4, and activation of LGALS9-HARVCR2 pathways. By deconvolution of bulk sequencing, the results of CIBERSORTx showed that the co-occurrence of ferroptosis tendency and EMT may lead to tumor metastasis and non-response to immunotherapy. Our findings showed there is a strong correlation between ferroptosis tendency and EMT. Ferroptosis may have a promotive effect on EMT. High propensities of ferroptosis and EMT may lead to poor prognosis and non-response to immunotherapy.

上皮间质转化（Epithelial-mesenchymal transition, EMT）与铁死亡（ferroptosis）是生物学领域的两类重要生命过程，在肿瘤细胞中二者存在紧密关联。本研究通过单细胞RNA测序，探究肺腺癌（LUAD）上皮细胞中EMT与铁死亡倾向之间的调控联系。我们利用Seurat工具处理GEO数据集GSE131907以构建表达矩阵，并提取上皮细胞组分。研究发现EMT进程与铁死亡倾向呈正相关。随后我们通过SCENIC分析差异激活的转录因子，并借助因果推断构建了分子调控有向网络。本研究发现部分铁死亡标志物（GPX4、SCP2、CAV1）对EMT具有较强的调控作用。通过iTALK构建细胞通讯网络后，结果显示Ferro_High_EMT_High细胞高表达SDC1、SDC4，且LGALS9-HARVCR2通路处于激活状态。对批量测序数据进行反卷积分析后，CIBERSORTx结果表明，铁死亡倾向与EMT共同发生可能会促进肿瘤转移，并导致免疫治疗无应答。本研究结果证实铁死亡倾向与EMT存在强相关性，铁死亡可能对EMT具有促进作用，而高铁死亡倾向与高EMT状态可能会导致不良预后及免疫治疗无应答。