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

Abstract

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.

Integrating Single-cell RNA-seq to construct a Neutrophil prognostic model for predicting immune responses in non-small cell lung cancer

“…The growth factor HBEGF, which is highly expressed in Monocytes, Neutrophils, Dendritic Cells, GMP Cells, Macrophages, and various Epithelial Cells, interacts with CD9 expressed in Cancer Cells to help mediate tumorigenesis and proliferation [38]. We also found that Cancer Cells interact with ITGB1, highly expressed in multiple cells such as Fibroblasts, Endothelial Cells, and Basal Cells, through angiogenesis signal molecules (VEGFA) to stimulate tumor growth and metastasis [39]. This discovery provides a new research idea for tumor immunotherapy.…”

Integrating Single-Cell RNA-seq to construct a Neutrophil prognostic model for predicting immune responses in non-small cell lung cancer

“…The growth factor HBEGF, which is highly expressed in Monocytes, Neutrophils, Dendritic Cells, GMP Cells, Macrophages, and various Epithelial Cells, interacts with CD9 expressed in Cancer Cells to help mediate tumorigenesis and proliferation [34]. We also found that Cancer Cells interact with ITGB1, highly expressed in multiple cells such as Fibroblasts, Endothelial Cells, and Basal Cells, through angiogenesis signal molecules (VEGFA) to stimulate tumor growth and metastasis [35]. This discovery provides a new research idea for tumor immunotherapy.…”

Bioinformatic analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease

“…In contrast to the protective effect in NAFLD, the published study has shown that SCP2 can promote the accumulation of low-density lipoprotein cholesterol (LDL-C) and reduce high-density lipoprotein cholesterol (HDL-C), promoting the development of atherosclerosis and hyperlipidemia [28]. And previous studies have indicated that SCP2 can inhibit ferroptosis poisoning inhibitors (GPX4 and cav1) and promote other ferroptosis poisoning drivers (PRKAA1, PRKAA2) [29]. MUC1 is a large O-type glycoprotein that is essential to maintain the function of epithelial cell surface [30].…”