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
英文原题:A tumor-infiltrating B lymphocytes -related index based on machine-learning predicts prognosis and immunotherapy response in lung adenocarcinoma.
A tumor-infiltrating B lymphocytes -related index based on machine-learning predicts prognosis and immunotherapy response in lung adenocarcinoma.
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。
我们的研究使用十种不同算法和 101 种算法组合开发了一个 BRI 模型。BRI 可能成为风险分层、预后和治疗方案选择的有价值工具。
肿瘤浸润性B淋巴细胞(TILBs)在塑造肿瘤免疫微环境(TIME)和肺腺癌(LUAD)进展中发挥关键作用。然而,全面系统地描述LUAD中TILBs特征的研究仍然匮乏。
研究采用GSE117570数据集的单细胞RNA测序来识别与TILBs相关的标志物。利用十种不同算法的综合机器学习方法,在TCGA、GSE31210和GSE72094数据集中构建了TILB相关指数(BRI)。我们使用多种算法评估了BRI与TIME以及免疫治疗相关生物标志物之间的关系。此外,我们在GSE91061和GSE126044两个数据集中评估了BRI在预测免疫治疗反应中的作用。
BRI作为LUAD的独立风险决定因素,展现出稳健且可靠的总体生存率预测能力。我们观察到高BRI评分组与低BRI评分组在B细胞、M2巨噬细胞、NK细胞和调节性T细胞评分上存在显著差异。值得注意的是,BRI与细胞毒性CD8+ T细胞浸润呈负相关(r = -0.43,p < 0.001),与调节性T细胞呈正相关(r = 0.31,p = 0.008)。我们还发现,与高BRI相比,低BRI患者更可能对免疫治疗产生应答,并与标准化疗和靶向治疗药物IC50值降低相关。此外,基于BRI的生存预测列线图在预测LUAD患者1年、3年和5年总体生存率方面展现出显著的临床应用前景。
INTRODUCTION: Tumor-infiltrating B lymphocytes (TILBs) play a pivotal role in shaping the immune microenvironment of tumors (TIME) and in the progression of lung adenocarcinoma (LUAD).
However, there remains a scarcity of research that has thoroughly and systematically delineated the characteristics of TILBs in LUAD. METHOD: The research employed single-cell RNA sequencing from the GSE117570 dataset to identify markers linked to TILBs. A comprehensive machine learning approach, utilizing ten distinct algorithms, facilitated the creation of a TILB-related index (BRI) across the TCGA, GSE31210, and GSE72094 datasets.
We used multiple algorithms to evaluate the relationships between BRI and TIME, as well as immune therapy-related biomarkers.
Additionally, we assessed the role of BRI in predicting immune therapy response in two datasets, GSE91061 and GSE126044. RESULT: BRI functioned as an independent risk determinant in LUAD, demonstrating a robust and reliable capacity to predict overall survival rates.
We observed significant differences in the scores of B cells, M2 macrophages, NK cells, and regulatory T cells between the high and low BRI score groups.
Notably, BRI was found to inversely correlate with cytotoxic CD8+ T-cell infiltration (r = -0. 43, p < 0. 001) and positively correlate with regulatory T cells (r = 0. 31, p = 0. 008).
We also found that patients with lower BRI were more likely to respond to immunotherapy and were associated with reduced IC50 values for standard chemotherapy and targeted therapy drugs, in contrast to higher BRI.
Additionally, the BRI-based survival prediction nomogram demonstrated significant promise for clinical application in predicting the 1-, 3-, and 5-year overall survival rates among LUAD patients. DISCUSSION: Our study developed a BRI model using ten different algorithms and 101 algorithm combinations. The BRI could be a valuable tool for risk stratification, prognosis, and selection of treatment approaches.
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 →
MEMBER ACCOUNT
登录成功会直接打开下一页。