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
外泌体 CCT3 作为肝细胞癌患者诊断和免疫治疗反应的生物标志物
英文原题：Exosomal CCT3 as a biomarker for diagnosis and immune therapy response in patients diagnosed with hepatocellular carcinoma.
查看英文原题
Exosomal CCT3 as a biomarker for diagnosis and immune therapy response in patients diagnosed with hepatocellular carcinoma.
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研究概要
外泌体 CCT3 是通过 MYC 通路激活和免疫浸润实现 HCC 诊断与 ICB 治疗的生物标志物。
中文摘要
背景
肝细胞癌（HCC）是最常见的肝癌类型，死亡率高，但缺乏用于诊断和预测免疫治疗应答的生物标志物。肿瘤来源外泌体中的致癌相关分子已用于筛选多种生物标志物。本研究旨在发现用于HCC诊断及预测免疫检查点阻断（ICB）治疗应答的新型生物标志物。
方法
整合癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和ExoCarta数据集，分析HCC与正常组织中的差异表达基因（DEG）。利用定量PCR、蛋白质印迹和免疫组化（IHC）验证HCC患者样本中CCT3的表达。
结果
外泌体CCT3被鉴定为具有重要意义的潜在生物标志物，并在不同肿瘤分期及癌旁正常组织中通过上述方法验证其表达。qPCR和IHC证实，CCT3表达显著增加HCC中活化NK 细胞的数量；CCT3表达还显著提高HCC免疫检查点的表达。HCC来源外泌体显著增加CCT3富集。
结论
外泌体CCT3可通过激活MYC通路和促进免疫细胞浸润，作为HCC诊断及预测ICB治疗应答的生物标志物。
展开英文摘要原文
BACKGROUND
Hepatocellular carcinoma (HCC) is the dominant type of liver cancer and is associated with a high mortality rate. However, HCC lacks biomarkers for diagnosis and immune therapy response. Tumor-derived exosomes (TDEs) carcinogen-specific molecules have been used for screening multiple biomarkers. This study aimed to identify new biomarkers for the diagnosis of HCC and response to immune checkpoint blockade (ICB) therapy.
METHODS
Analysis of differentially expressed genes (DEGs) in HCC and normal tissues was integrated using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ExoCarta datasets. The expression of CCT3 was validated in samples from patients with HCC using quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry (IHC) techniques.
RESULTS
Exosomal CCT3 was identified as a potential biomarker with significant impact. The expression of CCT3 in different tumor stages and normal tissues adjacent to the tumors (NATs) was validated using qPCR, western blotting, and IHC. CCT3 expression significantly increased the number of activated natural killer cells in HCC, as confirmed by qPCR and IHC. CCT3 expression significantly increases the expression of immune checkpoints in HCC. HCC-derived exosomes significantly increase the enrichment of CCT3.
CONCLUSION
Exosomal CCT3 is a biomarker for diagnosis and ICB therapy of HCC via MYC pathway activation and immune infiltration.
论文信息
- 作者
- Liu T、Cui Y、Ouyang Y、Wang M、Yue S
- 第一作者单位
- School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China; Nankai University Affiliated Eye Hospital, Nankai University, Tianjin, China; Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, China.China
- 通讯作者单位
- School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China. Electronic address: shijingyue@nankai.edu.cn.China
- 期刊
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver2025 Jun
- 原文标识
- PubMed 40221386 · DOI 10.1016/j.dld.2025.03.022