Cheng Xin, Wang Yadong, Liu Liangchao, Lv Chenggang, Liu Can, Xu Jingyun
General Surgery Department, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, China.
The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Front Mol Biosci. 2022 Apr 20;9:889688. doi: 10.3389/fmolb.2022.889688. eCollection 2022.
Ferroptosis induced by SLC7A11 has an important translational value in the treatment of cancers. However, the mechanism of SLC7A11 in the pathogenesis of colon adenocarcinoma (COAD) is rarely studied in detail. SLC7A11 expression was explored with The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, and Western blot assay. The correlation of SLC7A11 expression with the abundance of infiltrating immune cells was evaluated the TIMER database. The relation of SLC7A11 expression with immune cell markers was investigated Gene Expression Profiling Interactive Analysis (GEPIA). The co-expression genes of SLC7A11 were screened by R packages, and the PPI was constructed the STRING database. SLC7A11 and co-expressed gene modulators were selected by NetworkAnalyst and DSigDB database. The correlations between SLC7A11 and cancer immune characteristics were analyzed the TIMER and TISIDB databases. SLC7A11 is overexpressed in most tumors, including COAD. The expression level of SLC7A11 has a significant correlation with the infiltration levels of CD8 T cells, neutrophils, and dendritic cells in COAD. The infiltrated lymphocyte markers of Th1 cell such as TBX21, IL12RB2, IL27RA, STAT1, and IFN-γ were strongly correlated with SLC7A11 expression. Five hub genes co-expressed with SLC7A11 that induce ferroptosis were identified, and mir-335-5p, RELA, and securinine have regulatory effects on it. SLC7A11 was negatively correlated with the expression of chemokines and chemokine receptors, such as CCL17, CCL19, CCL22, CCL23, CXCL14, CCR10, CX3CR1, and CXCR3, in COAD. SLC7A11 may play a role in induced ferroptosis and regulating tumor immunity, which can be considered as potential therapeutic targets in COAD.
SLC7A11诱导的铁死亡在癌症治疗中具有重要的转化价值。然而，SLC7A11在结肠腺癌（COAD）发病机制中的作用机制鲜有详细研究。利用癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）以及蛋白质免疫印迹分析对SLC7A11的表达进行了探究。通过TIMER数据库评估SLC7A11表达与浸润免疫细胞丰度的相关性。利用基因表达谱交互分析（GEPIA）研究SLC7A11表达与免疫细胞标志物的关系。通过R包筛选SLC7A11的共表达基因，并利用STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络。通过NetworkAnalyst和DSigDB数据库选择SLC7A11及其共表达基因调节剂。利用TIMER和TISIDB数据库分析SLC7A11与癌症免疫特征之间的相关性。SLC7A11在包括COAD在内的大多数肿瘤中均有过表达。SLC7A11的表达水平与COAD中CD8 T细胞、中性粒细胞和树突状细胞的浸润水平显著相关。Th1细胞的浸润淋巴细胞标志物如TBX21、IL12RB2、IL27RA、STAT1和IFN-γ与SLC7A11表达密切相关。鉴定出五个与SLC7A11共表达且诱导铁死亡的枢纽基因，其中mir-335-5p、RELA和一叶萩碱对其具有调节作用。在COAD中，SLC7A11与趋化因子及趋化因子受体如CCL17、CCL19、CCL22、CCL23、CXCL14、CCR10、CX3CR1和CXCR3的表达呈负相关。SLC7A11可能在诱导铁死亡和调节肿瘤免疫中发挥作用，可被视为COAD潜在的治疗靶点。
