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:Construction of a novel disulfidptosis-related lncRNAs signature for prognosis prediction and anti-tumor immunity in laryngeal squamous cell carcinoma.
Construction of a novel disulfidptosis-related lncRNAs signature for prognosis prediction and anti-tumor immunity in laryngeal squamous cell carcinoma.
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二硫死亡作为一种与代谢功能障碍相关的创新性受控细胞死亡类型,已引起关注。然而,关于二硫死亡相关lncRNA(DRlncRNA)在喉鳞状细胞癌(LSCC)中的参与情况,目前知之甚少。
本研究旨在建立DRlncRNA特征,探讨其在LSCC中的预后价值,并探索其与免疫细胞亚群、生物信号通路的关联,以及探索其对药物敏感性的意义。
我们从癌症基因组图谱(TCGA)门户获取了LSCC患者的RNA-seq数据和相关临床数据,用于后续进一步分析。针对二硫死亡相关基因进行了文献检索。计算Pearson相关系数以鉴定DRlncRNA。对lncRNA进行了差异表达分析。利用单因素Cox回归分析,我们鉴定了二硫死亡相关预后lncRNA。采用LASSO-Cox回归分析对该组lncRNA进行优化,并构建二硫死亡相关lncRNA特征。采用多种统计技术评估模型预测性能。随后,根据DRlncRNA特征得出的风险评分对风险组进行分层。风险评分在LSCC患者预后预测中优于传统临床病理特征的优越性得到了证明。风险组之间出现了明显差异,尤其是在活化肥大细胞、嗜酸性粒细胞和活化NK细胞等免疫细胞亚群方面。
最后,低风险组对顺铂和吉西他滨等特定化疗药物的IC50值降低。体外实验表明我们的 DRlncRNAs 表现出差异性行为。DRlncRNAs 特征可作为稳健的生物标志物,能够预测 LSCC 患者的预后和治疗反应。
Disulfidptosis, an innovative type of controlled cellular death linked to metabolic dysfunction, has garnered attention.
However, there is limited knowledge regarding the involvement of disulfidptosisrelated lnRNAs (DRlncRNAs) in laryngeal squamous cell carcinoma (LSCC). The objective of our team in this study seeks to establish a DRlncRNAs signature, investigate their prognostic value in LSCC, and explore their associations with immune cell subpopulations, biological signaling pathways, and exploring implications for drug sensitivity.
We accessed LSCC patients' RNA-seq data and pertinent clinical data for subsequent further analysis from The Cancer Genome Atlas (TCGA) portal. A literature search was conducted focusing on disulfidptosis-related genes. Pearson correlation coefficients were calculated to identify DRlncRNAs. Differential expression analysis of lncRNAs was performed. Utilizing univariate Cox regression analysis, we identified disulfidptosis-associated prognostic lncRNAs. The LASSO-Cox regression analysis was employed to refine this set of lncRNAs and construct a disulfidptosis-related lncRNAs signature.
Various statistical techniques were employed to appraise model predictive performance. Subsequently, risk groups were stratified based on the risk score derived from the DRlncRNAs signature. The superiority of the risk score in prognostication over traditional clinicopathological features in LSCC patients was demonstrated. Evident distinctions emerged between risk groups, particularly in immune cell subpopulations like activated mast cells, eosinophils, and activated NK cells.
Finally, the low-risk group demonstrated reduced IC50 values for specific chemotherapeutics like cisplatin and gemcitabine. The in vitro experiments indicated differential behavior of our DRlncRNAs. The DRlncRNAs signature can serve as a robust biomarker with the ability to predict both prognosis and therapeutic responses among patients with LSCC.
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