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:Innate immune cell barrier-related genes inform precision prognosis in pancreatic cancer.
Innate immune cell barrier-related genes inform precision prognosis in pancreatic cancer.
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本研究建立了 CDRG-RSF 模型,这是一种利用先天免疫基因的稳健预后工具。
从KEGG、ImmPort、MSigDB和InnateDB整理先天免疫细胞屏障相关基因。利用TCGA和GTEx数据集开展差异表达分析。通过单变量Cox回归识别与生存相关的基因。使用14种机器学习算法构建PC预后模型,并通过长期生存指标、功能富集、免疫浸润分析和药物敏感性谱进行验证。采用“mime1”程序包筛选核心基因,并利用单细胞RNA测序(scRNA-seq)数据探究UBASH3B的功能。
共识别352个先天免疫细胞屏障相关差异表达基因,其中NK细胞通路与PC免疫相关。单变量Cox分析发现8个保护性基因和84个风险基因。基于风险基因训练的随机生存森林(RSF)模型对3年和5年生存具有良好预测能力。高风险患者肿瘤突变负荷(TMB)较高、NK/CD8⁺ T细胞浸润较低,对厄洛替尼和奥沙利铂耐药,但对5-氟尿嘧啶敏感。研究突出5个关键基因:ITGB6、COL17A1、MMP28、DIAPH3和UBASH3B。UBASH3B是一种新型标志物,与NK细胞活化负相关,并介导免疫信号和药物耐药。讨论:本研究建立了CDRG-RSF模型,这是一种利用先天免疫基因的稳健预后工具。UBASH3B在免疫抑制和药物耐药中的双重作用,凸显其用于将PC患者分层并匹配治疗的潜力。结果强调,整合机器学习与免疫分析有助于推动PC精准肿瘤学发展。
Innate immune cell barrier-related genes were curated from KEGG, ImmPort, MSigDB, and InnateDB. Differential expression analysis was performed using TCGA and GTEx datasets. Univariate Cox regression identified survival-associated genes. Prognostic modeling of PC was developed using 14 machine learning algorithms, with performance validated through long-term survival metrics, functional enrichment, immune infiltration analysis, and drug sensitivity profiling. Core genes were prioritized via the "mime1" package, and single-cell RNA sequencing (scRNA-seq) data explored UBASH3B's functional role.
352 differentially expressed genes of Innate immune cell barrier-related were identified, with NK cell pathways linked to PC immunity. Univariate Cox analysis revealed 8 protective and 84 risk genes. The RSF model (trained on risk genes) showed strong 3- and 5-year survival prediction. High-risk patients exhibited elevated tumor mutation burden (TMB), reduced NK/CD8+ T cell infiltration, and resistance to Erlotinib/Oxaliplatin but sensitivity to 5-Fluorouracil. Five key genes (ITGB6, COL17A1, MMP28, DIAPH3, UBASH3B) were highlighted. UBASH3B, a novel marker, correlated negatively with NK cell activation and mediated immune signaling and drug resistance. DISCUSSION: This study established the CDRG-RSF model, a robust prognostic tool leveraging innate immune genes. UBASH3B's dual role in immune suppression and drug resistance highlights its potential for stratifying PC patients into tailored treatment groups. The findings underscore the importance of integrating machine learning with immune profiling to advance precision oncology for PC.
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