RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
铜死亡相关基因 FDX1 高表达与结肠腺癌（COAD）良好预后及免疫细胞浸润相关
英文原题：High expression of cuproptosis-related gene FDX1 in relation to good prognosis and immune cells infiltration in colon adenocarcinoma (COAD).
查看英文原题
High expression of cuproptosis-related gene FDX1 in relation to good prognosis and immune cells infiltration in colon adenocarcinoma (COAD).
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研究概要
FDX1 在诱导铜死亡和调节肿瘤免疫中发挥作用，可作为 COAD 的潜在治疗靶点。
研究思路结论见上方概要
背景
FDX1诱导的铜死亡是一种新发现的调节细胞死亡的机制。然而，FDX1在结肠腺癌（COAD）发病机制中的作用仍有待研究。
方法
通过癌症基因组图谱（TCGA）数据库和人类蛋白质图谱（HPA）数据库分析FDX1表达。通过Kaplan-Meier（KM）生存曲线研究FDX1表达与COAD预后之间的关联。使用R包筛选FDX1的差异表达基因（DEGs），并通过STRING数据库构建PPI。使用Cytoscape软件检测PPI网络中最显著的模块。使用CancerSEA数据库分析FDX1表达水平对COAD细胞不同功能状态的影响。通过TIMER2.0数据库分析FDX1表达与COAD免疫浸润之间的关系。通过Western blot检测FDX1高表达的COAD患者，并通过流式细胞术测量免疫浸润水平。
结果
FDX1在大多数癌症中低表达，如BRCA、KICH和COAD。FDX1高表达的COAD患者的总生存期（OS）和疾病特异性生存期（DSS）优于低表达组。GO-KEGG富集分析显示，FDX1及其共表达基因在COAD的发病机制中发挥重要作用。此外，COAD中FDX1表达与“静息”和“炎症”呈正相关，但与“侵袭”呈负相关。FDX1表达与CD8 + T细胞、NK细胞和中性粒细胞的浸润水平呈正相关。相反，FDX1表达与CD4 + T细胞和癌症相关成纤维细胞（CAFs）呈负相关。最后，筛选出6例FDX1高表达的COAD患者，这些患者癌组织中CD8 + T细胞比例显著高于癌旁组织，而CD4 + T细胞则呈现相反模式。
展开英文摘要原文
BACKGROUND
Cuproptosis induced by FDX1 is a newly discovered mechanism regulating cell death. However, the role of FDX1 in the pathogenesis of colon adenocarcinoma (COAD) remains to be studied.
METHODS
FDX1 expression was analyzed with The Cancer Genome Atlas (TCGA) database and Human Protein Atlas (HPA) database. Association between FDX1 expression and COAD prognosis was investigated via the Kaplan-Meier (KM) survival curve. The differentially expressed genes (DEGs) of FDX1 were screened with R packages and the PPI were constructed via STRING database. Cytoscape software was used to detect the most profound modules in the PPIs network. CancerSEA database was used to analyze the effect of FDX1 expression levels on different functional status of COAD cells. The relationship between FDX1 expression and immune infiltration of COAD was analyzed by TIMER2.0 database. The COAD patients with high expression of FDX1 by Western blot, and the levels of immune infiltration were measured by flow cytometry.
RESULTS
FDX1 was low expressed in most cancers, such as BRCA, KICH, and COAD. The overall survival (OS) and disease-specific survival (DSS) of COAD with high FDX1 expression were better than that of the low expression group. GO-KEGG enrichment analysis revealed that FDX1 and its co-expressed genes played an important role in the pathogenesis of COAD. Moreover, FDX1 expression in COAD were positively associated with "quiescence" and "inflammation" but negatively correlated with "invasion". FDX1 expression was positively correlated with infiltration levels of CD8 + T cells, NK cells, and neutrophils. Oppositely, FDX1 expression was negatively correlated with that of CD4 + T cells and cancer-associated fibroblasts (CAFs). Finally, 6 COAD patients with high expression of FDX1 were screened, and the proportion of CD8 + T cells in cancer tissues of these patients was significantly higher than that in paracancerous, while the CD4 + T cells presented the opposite pattern.
CONCLUSION
FDX1 plays a role in inducing cuproptosis and modulating tumor immunity, which could be considered as potential therapeutic targets in COAD.
论文信息
- 作者
- Wang L、Cao Y、Guo W、Xu J
- 第一作者单位
- General Practice Department, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, China.China
- 通讯作者单位
- School of Basic Medicine, Wannan Medical College, NO. 22 Wenchang west road, Wuhu, Anhui Province, China. 20200011@wnmc.edu.cn.China
- 期刊
- Journal of cancer research and clinical oncology2023 Jan
- 原文标识
- PubMed 36173462 · DOI 10.1007/s00432-022-04382-7
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