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
FANCD2 作为与乙型肝炎相关肝细胞癌免疫和药物治疗相关的新型预后生物标志物
英文原题：FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma.
查看英文原题
FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma.
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研究概要
我们的研究表明，FANCD2 是抗乙型肝炎相关 HCC 的潜在新型生物标志物和免疫治疗靶点，这可能与索拉非尼的化疗反应有关。
研究思路结论见上方概要
背景
铁死亡与肿瘤的免疫抑制相关，并在癌症进展中发挥关键作用。范可尼贫血互补群D2（FANCD2）是调控铁死亡的重要基因。然而，FANCD2在乙型肝炎相关肝细胞癌（HCC）中的作用机制尚不清楚。在本研究中，我们探讨了FANCD2在乙型肝炎相关HCC中的预后意义及其作用机制。
方法
利用癌症基因组图谱（TCGA）探索了 FANCD2 在乙型肝炎相关 HCC 中的表达，并使用基因表达综合数据库（GEO）进行了验证。采用单因素和多因素 Cox 回归分析以及 Kaplan-Meier 生存曲线分析 FANCD2 表达与乙型肝炎相关 HCC 患者总生存期之间的关系。使用 STRING 网站构建了 FANCD2 的蛋白质-蛋白质相互作用网络。此外，还分析了 FANCD2 表达与干性指数、肿瘤突变负荷、微卫星不稳定性（MSI）、免疫通路、铁代谢相关基因以及索拉非尼化疗反应之间的相关性。
结果
我们的结果表明，FANCD2在乙型肝炎相关HCC中显著过表达，并对该疾病的诊断（AUC，0.903）和预后表现出很强的预测能力。FANCD2高表达与乙型肝炎相关HCC的不良预后、高级别肿瘤、PDL-1高表达、高MSI评分和低索拉非尼IC50相关。BRCA1、BRCA2、FAN1和FANCC是与FANCD2相互作用的重要蛋白。FANCD2的表达水平与乙型肝炎相关HCC中Treg细胞、B细胞、CD8 + T细胞、CD4 + T细胞、中性粒细胞、巨噬细胞、髓系树突状细胞和NK细胞的浸润水平显著相关。FANCD2与肿瘤增殖特征通路、DNA修复和细胞对缺氧的反应呈正相关。
展开英文摘要原文
BACKGROUND
Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC.
METHODS
The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan-Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein-protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed.
RESULTS
Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia.
CONCLUSION
Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.
论文信息
- 作者
- Tang X、Luo B、Huang S、Jiang J、Chen Y、Ren W、Shi X、Zhang W
- 第一作者单位
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, China.China
- 通讯作者单位
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, China. lvmuhan@swmu.edu.cn.China
- 期刊
- European journal of medical research2023 Oct 11
- 原文标识
- PubMed 37821996 · DOI 10.1186/s40001-023-01411-0
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