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:Establishment and Validation of an Interferon-Stimulated Genes (ISGs) Prognostic Signature in Pan-cancer Patients: A Multicenter, Real-world Study.
Establishment and Validation of an Interferon-Stimulated Genes (ISGs) Prognostic Signature in Pan-cancer Patients: A Multicenter, Real-world Study.
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本研究旨在开发一种干扰素刺激基因(ISG)特征,以预测癌症患者总生存期(OS),共纳入5643名泛癌患者。采用微阵列数据线性模型分析方法,在全体ISG家族中识别差异表达的预后相关基因。利用时间依赖性受试者工作特征(ROC)和Kaplan-Meier生存分析,检验多基因特征预测泛癌患者预后的效能。并在独立泛癌队列中通过实时定量PCR验证该基因特征的预后表现及潜在生物学功能。最终筛选出3个ISG基因构建分类器和特定风险评分公式,据此将患者分为低危组和高危组。时间依赖性ROC分析证明其预后准确性,并在7个外部验证队列中验证了预后价值。研究还构建了列线图,以指导肺腺癌患者个体化治疗。生物学通路和肿瘤免疫浸润分析显示,该特征可能通过阻断NK细胞活化导致不良预后。最后,我们通过本中心样本的实时定量PCR确认了这一特征。研究发现了一种稳健的ISG相关特征,可有效将泛癌患者分为OS不同的亚组。
Our study aims at developing an interferon-stimulated genes (ISGs) signature that could predict overall survival (OS) in cancer patients, which enrolled a total of 5643 pan-cancer patients. Linear models for microarray data method analysis were conducted to identify the differentially expressed prognostic genes in the global ISGs family. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival analysis were used to test the efficiency of a multi-gene signature in predicting the prognosis of pan-cancer patients. The prognostic performance and potential biological function of gene signature were verified by quantitative real-time PCR in a pan-cancer independent cohort.
Three ISGs genes were finally identified to build a classifier, a specific risk score formula, with which patients were classified into the low- or high-risk groups. Time-dependent ROC analyses proved prognostic accuracy. Then, its prognostic value was validated in seven external validation series. A nomogram was constructed to guide the individualized treatment of patients with lung adenocarcinoma. Biological pathway and tumor immune infiltration analysis showed that the signature might cause poor prognosis by blocking NK cell activation.
Finally, the signature in our centers was confirmed by real-time quantitative PCR. A robust ISGs-related feature was discovered to effectively classify pan-cancer patients into subgroups with different OS.
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