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
筛选和鉴定多功能蛋白聚糖作为基底细胞癌的敏感生物标志物和潜在治疗靶点
英文原题：Screening and identification of versican as a sensitive biomarker and potential therapeutic target in basal cell carcinoma.
查看英文原题
Screening and identification of versican as a sensitive biomarker and potential therapeutic target in basal cell carcinoma.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
基底细胞癌（BCC）是最常见的非黑色素瘤皮肤癌（NMSC）。然而，目前用于BCC诊断的生物标志物很少。本研究旨在通过转录组和发病机制研究，发现用于诊断和治疗的新型BCC生物标志物。从基因表达综合数据库（GEO）下载BCC组织的微阵列数据集，并鉴定差异表达基因（DEGs）。从GSE125285和GSE42109数据集中，共鉴定出558个在BCC与正常样本之间差异表达的DEGs。其中69个DEGs以组织/器官特异性方式表达，最终鉴定出三个组织特异性关键基因。这三个基因在BCC诊断中表现出高性能，AUC≥0.8，表明它们具有较高的诊断意义。CIBERSORT分析显示，BCC患者免疫微环境中静息NK细胞、M1巨噬细胞增加，树突状细胞减少。
此外，versican（VCAN）可能参与皮肤癌中M1巨噬细胞的极化。当VCAN被敲低后，皮肤癌细胞系A431的增殖、迁移和侵袭能力减弱。
同时，关键致癌因子DDX5的表达也降低，并通过BAX/BCL-2/c-Caspase3通路促进凋亡。裸鼠细胞源性异种移植模型研究表明，与对照肿瘤细胞相比，敲低肿瘤细胞中的VCAN显著抑制了肿瘤大小，提示VCAN是肿瘤发生的重要基因之一。
同时，我们检测了细胞源性异种移植小鼠模型肿瘤样本中巨噬细胞M1极化的水平，与对照组相比，VCAN敲低显著降低了巨噬细胞M1极化。
我们还检测了BCC患者肿瘤样本中VCAN的表达，并证实BCC中VCAN的表达显著高于正常皮肤组织。因此，VCAN可能成为BCC诊断和治疗的潜在临床靶点。
展开英文摘要原文
Basal cell carcinoma (BCC) is the most common type of non-melanoma skin cancer (NMSC).
However, few biomarkers have been developed for the diagnosis of BCC.
This study aimed to uncover novel BCC biomarkers for diagnosis and treatment via transcriptome and pathogenesis investigations. Microarray datasets of BCC tissues were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. A total of 558 DEGs were identified between BCC and normal samples from the GSE125285 and GSE42109 datasets.
69 DEGs were expressed in a tissue/organ-specific manner, of which three tissue-specific key genes were finally identified. The three genes showed high performance for BCC diagnosis with AUCs of ≥0. 8, indicating that they have high diagnostic significance. CIBERSORT analysis revealed an increase in resting NK cells, M1 macrophages and a decrease in dendritic cells in the immune microenvironment of BCC patients.
In addition, versican (VCAN) may be involved in the polarization of M1 macrophages in skin cancer. When VCAN was knocked down, the skin cancer cell line A431 was weakened in terms of proliferation, migration and invasion. Meanwhile, the expression of the key oncogenic factors DDX5 was also reduced and apoptosis was promoted through the BAX/BCL-2/c-Caspase3 pathway.
The cell-derived xenograft model study in nude mice showed that knockdown of VCAN in tumour cells significantly suppressed tumour size compared to control tumour cells, suggesting that VCAN is one of the important genes for tumourigenesis. Meanwhile, we examined the level of macrophage M1 polarization in tumour samples from a cell-derived xenograft mouse model, and VCAN knockdown significantly reduced macrophage M1 polarization compared to controls.
We also detected the expression of VCAN in tumour samples from BCC patients and verified that VCAN expression was significantly higher in BCC than in normal skin tissue.
Thus, VCAN could be a potential clinical target for the diagnosis and treatment of BCC.
论文信息
- 作者
- Li W、Wang Y、Hu Q、Li S、Guo D、Liu L、Huang X、Dou L
- 单位
- Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.China
- 期刊
- International journal of medical sciences2025
- 原文标识
- PubMed 40386063 · DOI 10.7150/ijms.105650
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →