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
整合分析鉴定线粒体核糖体蛋白 MRPL3 为胰腺癌潜在预后生物标志物和治疗靶点
英文原题：An integrated analysis identified mitochondrial ribosomal protein MRPL3 as a potential prognostic biomarker and therapeutic target in pancreatic cancer.
查看英文原题
An integrated analysis identified mitochondrial ribosomal protein MRPL3 as a potential prognostic biomarker and therapeutic target in pancreatic cancer.
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
线粒体在肿瘤代谢中发挥着至关重要的作用。线粒体核糖体蛋白L3（MRPL3）是线粒体核糖体的核心成分。然而，其在胰腺癌（PC）中的作用仍不清楚。
我们研究了 MRPL3 在 PC 中的生物学功能和潜在机制。使用公共数据库分析 MRPL3 的表达。使用 Kaplan-Meier 生存分析和单变量/多变量 Cox 回归评估预后意义。进行功能富集分析以确定 MRPL3 相关信号通路。
此外，还进行了免疫细胞浸润和肿瘤突变负荷（TMB）分析，以探讨MRPL3表达与肿瘤微环境之间的关系。使用肿瘤免疫功能障碍和排斥 (TIDE) 评分和药物敏感性分析来评估 MRPL3 的治疗意义。进行蛋白质印迹和免疫组织化学 (IHC) 以验证 MRPL3 表达并评估其在临床 PC 样本中的预后意义。进行体外实验以确定 MRPL3 沉默对 PC 细胞行为的影响。MRPL3 表达在 PC 中显着增加，并且与公共队列中的不良预后相关。功能富集和免疫浸润分析表明，MRPL3 高表达与 G2/M DNA 检查点损伤、Th2 细胞浸润增加和自然杀伤 (NK) 细胞活性降低相关。
此外，高 MRPL3 表达对应于较低的免疫治疗敏感性和较高的化疗敏感性。IHC 分析证实，MRPL3 高表达与 PC 的总生存期显着缩短相关（风险比 [HR] = 2.13，95% 置信区间 [CI] = 1.35-3.34，p = 0。001）。体外实验表明，MRPL3敲除显着抑制PC增殖、迁移和侵袭。MRPL3 促进 PC 进展、免疫逃避和治疗耐药，导致不良预后。它可能作为一种有前途的生物标志物和个体化治疗策略的潜在目标。
展开英文摘要原文
Mitochondria play a crucial role in tumor metabolism. Mitochondrial ribosomal protein L3 (MRPL3) is a core component of the mitochondrial ribosome.
However, its role in pancreatic cancer (PC) remains unclear.
We investigated the biological functions and underlying mechanisms of MRPL3 in PC. The expression of MRPL3 was analyzed using public databases. Prognostic significance was evaluated using Kaplan-Meier survival analysis and univariate/multivariate Cox regression. Functional enrichment analysis was performed to identify MRPL3-associated signaling pathways.
In addition, immune cell infiltration and tumor mutational burden (TMB) analyses were conducted to explore the relationship between MRPL3 expression and the tumor microenvironment. Tumor immune dysfunction and exclusion (TIDE) scores and drug sensitivity analyses were used to assess the therapeutic implications of MRPL3. Western blotting and immunohistochemistry (IHC) were performed to validate MRPL3 expression and evaluate their prognostic significance in clinical PC samples.
In vitro experiments were performed to determine the effects of MRPL3 silencing on PC cell behavior. MRPL3 expression was notably increased in PC and associated with an unfavorable prognosis in public cohorts. Functional enrichment and immune infiltration analyses revealed that high MRPL3 expression was associated with damage to the G2/M DNA checkpoint, increased Th2 cell infiltration, and reduced natural killer (NK) cell activity.
Furthermore, high MRPL3 expression corresponded to lower immunotherapy sensitivity and higher chemotherapy sensitivity. The IHC analysis confirmed that high MRPL3 expression is associated with significantly shorter overall survival in PC (hazard ratio [HR] = 2. 13, 95% confidence interval [CI] = 1. 35-3. 34, p = 0. 001).
In vitro experiments demonstrated that MRPL3 knockout significantly suppressed PC proliferation, migration, and invasion. MRPL3 promotes PC progression, immune evasion, and therapeutic resistance, contributing to an unfavorable prognosis. It may serve as a promising biomarker and potential target for individualized treatment strategies.
论文信息
- 作者
- Yang W、Deng H、Pan T、Zhang X、Peng L、Wang S
- 第一作者单位
- Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.China
- 通讯作者单位
- Department of General Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.China
- 期刊
- Journal of Cancer2025
- 原文标识
- PubMed 40740231 · DOI 10.7150/jca.114067
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 →