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:Prognostic Model for Clear-cell Renal Cell Carcinoma Based on Natural Killer Cell-related Genes.
Prognostic Model for Clear-cell Renal Cell Carcinoma Based on Natural Killer Cell-related Genes.
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NKRPS 对 ccRCC 患者的预后具有很强的预测能力,这可能有助于个体化治疗和医疗决策。
自然杀伤(NK)细胞是影响透明细胞肾细胞癌(ccRCC)进展和免疫监视的关键因素。本研究旨在构建NK 细胞相关预后特征(NKRPS),以预测ccRCC患者的结局,并为寻找合适的治疗策略提供指导。
从TCGA和ArrayExpress数据库中,下载了TCGA队列(n = 515)和E-MTAB-1980队列(n = 101)中ccRCC患者的转录组谱和相关临床信息。通过单因素Cox分析和LASSO-Cox回归算法,构建了一个NKRPS以评估患者的预后。绘制受试者工作特征(ROC)曲线和校准曲线以评估预后模型的预测能力。然后,对ccRCC患者的肿瘤微环境(TME)、肿瘤突变负荷(TMB)、免疫检查点抑制剂(ICIs)治疗和靶向药物治疗的敏感性进行了分析。
鉴定出9个基因(BID、CCL7、CSF2、IL23A、KNSTRN、RHBDD3、PIK3R3、RNF19B和VAV3)用于构建NKRPS。高风险组相比低风险组显示出不良生存(P < .05)。此外,ROC曲线在1年、3年和5年的曲线下面积(AUC)分别为0.766、0.755和0.757。高风险组的特征为免疫浸润更优、TMB更高,以及5个ICI相关基因表达更高。此外,该模型能够预测患者对化疗药物的敏感性。
Natural killer (NK) cells are a key factor affecting progression and immune surveillance of clear-cell renal cell carcinoma (ccRCC). This study sought to construct a natural killer cell-related prognostic signature (NKRPS) to predict the outcome of ccRCC patients and to furnish guidance for finding appropriate treatment strategies.
From the TCGA and ArrayExpress databases, transcriptomic profiles and relevant clinical information of ccRCC patients were downloaded for the TCGA cohort (n = 515) and the E-MTAB-1980 cohort (n = 101). With the univariate Cox analysis and LASSO-Cox regression algorithm, a NKRPS was built to evaluate patients' prognosis. Receiver operating characteristic (ROC) curves and calibration curves were drawn to estimate the predictive power of the prognostic model. Then, tumor microenvironment (TME), tumor mutational burden (TMB), sensitization to immune checkpoint inhibitors (ICIs) therapy and targeted drug treatment were analyzed in ccRCC patients.
Nine genes (BID, CCL7, CSF2, IL23A, KNSTRN, RHBDD3, PIK3R3, RNF19B and VAV3) were identified to construct a NKRPS. High-risk group displayed undesirable survival compared to low-risk group (P < .05). Moreover, the area under the curve (AUC) of ROC at 1-, 3- and 5-year were 0.766, 0.755, and 0.757, respectively. High-risk group was characterized by superior immune infiltration, higher TMB, and higher expression of 5 ICI-related genes. Additionally, this model enabled to predict the sensitivity of patients to chemotherapy drugs.
NKRPS had a strong predictive power on prognosis of ccRCC patients, which may facilitate individualized treatment and medical decision making.
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