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:Multiphase enhanced computed tomography features captured by delta radiomics reveal prognosis and tumor heterogeneity in patients with hepatocellular carcinoma treated with transarterial chemoembolization.
Multiphase enhanced computed tomography features captured by delta radiomics reveal prognosis and tumor heterogeneity in patients with hepatocellular carcinoma treated with transarterial chemoembolization.
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基于多期增强 CT 的 delta 影像组学模型能够准确预测接受 TACE 治疗的 HCC 患者的预后,并反映肿瘤异质性,有助于制定治疗计划。
尽管经动脉化疗栓塞(TACE)是中期肝细胞癌(HCC)广泛使用的局部区域治疗,但患者间的治疗反应存在显著异质性。本研究旨在开发基于治疗前增强计算机断层扫描(CT)的delta影像组学模型,以预测接受TACE的HCC患者的预后并揭示肿瘤异质性。
共纳入2016年1月至2020年6月期间在两个医疗中心接受TACE治疗的269例患者,分为三个队列:训练队列(n = 126)、内部验证队列(n = 84)、外部测试队列(n = 59)。在治疗前CT的多个期相上提取肿瘤区域的影像学特征,并通过最小绝对收缩和选择算子Cox(LASSO-Cox)回归算法预测无进展生存期(PFS)。使用Kaplan-Meier曲线评估总生存期(OS)。在23例来自癌症基因组图谱(TCGA)的CT患者中,分析了与TACE预后相关的基因和肿瘤微环境差异。使用来自综合基因表达综合数据库(GEO)公共数据库的单细胞数据,探索不同基因在细胞中的表达。
在接受TACE治疗的患者中,delta影像组学模型预测2年PFS的受试者工作特征曲线下面积在训练队列、内部验证队列和外部测试队列中分别为0.812、0.720和0.807。Rad-score基于通过LASSO筛选的影像组学特征计算。Rad-score将患者分为高风险组和低风险组,在所有队列中OS差异均有统计学意义。高风险组的免疫评分更高。值得注意的是,在免疫浸润分析中,不同风险组之间B细胞、静息CD4记忆T细胞、活性NK 细胞和肥大细胞存在显著差异。
Although transarterial chemoembolization (TACE) is a widely used locoregional therapy for intermediate-stage hepatocellular carcinoma (HCC), there is substantial inter-patient heterogeneity in treatment response. This study aimed to develop a delta radiomic model based on pre-treatment enhanced computed tomography (CT) to predict the prognosis of HCC patients undergoing TACE and to reveal tumor heterogeneity.
A total of 269 patients treated with TACE between January 2016 and June 2020 were enrolled from two medical centers and divided into three cohorts: a training cohort (n = 126), an internal validation cohort (n = 84), an external test cohort (n = 59). Radiological features of the tumor area were extracted on multiple phases of CT before treatment, and progression-free survival (PFS) was predicted through the least absolute shrinkage and selection operator Cox (LASSO-Cox) regression algorithm. Overall survival (OS) was evaluated using the Kaplan-Meier curve. Genetic and tumor microenvironment differences related to the prognosis of TACE were analyzed in 23 patients with CT from The Cancer Genome Atlas (TCGA). Single-cell data from the comprehensive Gene Expression Omnibus (GEO) public database were used to explore the expression of different genes in cells.
The area under the receiver operating characteristic curves of the delta radiomic model for predicting 2-year PFS in TACE-treated patients were 0.812, 0.720, and 0.807 in the training, internal validation, and external test cohorts, respectively. The Rad-score was calculated based on radiomic features selected through LASSO. The Rad-score stratified patients into high- and low-risk groups, with significant differences in OS across all cohorts. The high-risk group had a higher immune score. It is worth noting that in the immune infiltration analysis, there were significant differences in B cells, resting CD4 memory T cells, active natural killer cells, and mast cells among different risk groups.
The delta radiomics model based on multiphase enhanced CT accurately predicts prognosis and reflects tumor heterogeneity in HCC patients treated with TACE, and contributes to treatment planning.
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