Intra-Tumoral Expression of SLC7A11 Is Associated with Immune Microenvironment, Drug Resistance, and Prognosis in Cancers: A Pan-Cancer Analysis

作者：Jiajun He, Hongjian Ding, Huaqing Li, Zhiyu Pan, Qian Chen · 发表于：Frontiers in Genetics · 年份：2021 · DOI：10.3389/fgene.2021.770857 · 被引用次数：72 · 研究领域：Ferroptosis and cancer prognosis、Epigenetics and DNA Methylation、RNA modifications and cancer

While many anti-cancer modalities have shown potent efficacy in clinical practices, cancer prevention, timely detection, and effective treatment are still challenging. As a newly recognized iron-dependent cell death mechanism characterized by excessive generation of lipid peroxidation, ferroptosis is regarded as a potent weapon in clearing cancer cells. The cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) is the core target for ferroptosis regulation, the overexpression of which dictates downregulated sensitivity to ferroptosis in cancer cells. Hence, we elaborated the pan-cancer level bioinformatic study and systematically elucidated the role of intra-tumoral expression of SLC7A11 in the survival of cancer patients and potential immunotherapeutic response. Specifically, 25/27 (92.6%) cancers were featured with upregulated SLC7A11 expression, where SLC7A11 overexpression is a risk factor for worse overall survival in 8 cancers. We also validated SLC7A11 expression in multiple pancreatic cancer cell lines in vitro and found that it was upregulated in most pancreatic cancer cell lines ( p < 0.05). Single-cell sequencing method revealed the SLC7A11 was majorly expressed in cancer cells and mononuclear cells. To further explore the function of SLC7A11 in cancer progression, we analyzed the influence on cell proliferation after the knockdown or knockout of SLC7A11 by either CRISPR or RNAi methods. Besides, the association between SLC7A11 and drug res...