肝细胞癌中与树突状细胞相关的基因信号：预后和疗效评估分析
IF 4.2
3区 医学
Q2 ONCOLOGY
引用次数: 0
摘要
背景：本研究旨在鉴定肝细胞癌（HCC）患者的树突状细胞（DCs）相关基因，建立DC相关亚型和特征，并将其与预后和治疗反应相关联：根据TCGA（374个样本）、GSE14520（242个样本）和GSE76427数据集（115个样本）中的RNA测序结果，采用加权基因共表达网络分析（WGCNA）筛选了DC相关基因，并采用TIME方法评估了免疫浸润情况。通过无监督聚类，确定了两种与 HCC 中 DC 相关的亚型。利用 LASSO 和 Cox 回归模型构建了可预测总生存期的 DC 相关特征（DCRS），并在三个数据集中进行了验证。此外，还探讨了DCRS风险组的基因突变特征、免疫浸润水平和治疗敏感性。在广西队列中接受联合靶向治疗和免疫治疗的13例HCC患者的转录组中，使用Wilcoxon检验验证了DCRS基因的表达水平和风险评分：结果：由13个与DCs相关的基因组成的特征被构建出来，低DCRS风险组的预后一致性在TCGA（P=0.003）、GSE76427（P=0.005）和GSE14520（P=0.047）数据集中得到了验证。此外，在147个样本的经动脉化疗栓塞（TACE）治疗数据集GSE104580中，应答组的风险评分低于非应答组（P=0.01），而在140个样本的索拉非尼治疗数据集GSE109211（P=0.041）和17个样本的抗PD-1治疗数据集GSE202069（P=0.027）中，应答组的风险评分更高。我们还验证了DCRS的基因表达水平和广西队列中应答组较高的风险评分（P=0.034）：结论：在HCC中建立了由13个基因组成的DCRS，有助于预测患者的预后以及对TACE、靶向治疗和免疫治疗的反应性。本文章由计算机程序翻译，如有差异，请以英文原文为准。
Dendritic Cell-Related Gene Signatures in Hepatocellular Carcinoma: An Analysis for Prognosis and Therapy Efficacy Evaluation
Background: This study aimed to identify dendritic cells (DCs) related genes in hepatocellular carcinoma (HCC) patients, establish DC-related subtypes and signatures, and correlate them with prognosis and treatment response.
Methods: DC-related genes were screened using Weighted Gene Co-expression Network Analysis (WGCNA) based on RNA sequencing from the TCGA (374 samples), GSE14520 (242 samples), and GSE76427 datasets (115 samples), following immune infiltration assessment by the TIME method. Two DC-related subtypes in HCC were identified through unsupervised clustering. A DC-related signature (DCRS) predictive of overall survival was constructed using LASSO and Cox regression models, and validated across the three datasets. Additionally, genetic mutation characteristics, immune infiltration levels, and treatment sensitivity were explored in DCRS risk groups. The expression levels of DCRS genes and risk scores were validated in the transcriptome of 13 HCC patients receiving combined targeted therapy and immunotherapy in the Guangxi cohort using Wilcoxon test.
Results: A signature consisting of 13 genes related to DCs was constructed, and the superior prognostic consistency of the low DCRS risk group was validated across the TCGA (P=0.003), GSE76427 (P=0.005), and GSE14520 (P=0.047) datasets. Furthermore, in the 147-sample transarterial chemoembolization (TACE) treatment dataset GSE104580, the response group exhibited lower risk scores than the non-response group (P=0.01), whereas in the 140-sample Sorafenib treatment dataset GSE109211 (P=0.041) and the 17-sample anti-PD-1 treatment dataset GSE202069 (P=0.027), the risk scores were higher in the response group. We also validated the gene expression levels of DCRS and the higher risk scores in the response group of the Guangxi cohort (P=0.034).
Conclusion: A DCRS consisting of 13 genes was established in HCC, facilitating the prediction of patient prognosis and responsiveness to TACE, targeted therapy, and immunotherapy.
Methods: DC-related genes were screened using Weighted Gene Co-expression Network Analysis (WGCNA) based on RNA sequencing from the TCGA (374 samples), GSE14520 (242 samples), and GSE76427 datasets (115 samples), following immune infiltration assessment by the TIME method. Two DC-related subtypes in HCC were identified through unsupervised clustering. A DC-related signature (DCRS) predictive of overall survival was constructed using LASSO and Cox regression models, and validated across the three datasets. Additionally, genetic mutation characteristics, immune infiltration levels, and treatment sensitivity were explored in DCRS risk groups. The expression levels of DCRS genes and risk scores were validated in the transcriptome of 13 HCC patients receiving combined targeted therapy and immunotherapy in the Guangxi cohort using Wilcoxon test.
Results: A signature consisting of 13 genes related to DCs was constructed, and the superior prognostic consistency of the low DCRS risk group was validated across the TCGA (P=0.003), GSE76427 (P=0.005), and GSE14520 (P=0.047) datasets. Furthermore, in the 147-sample transarterial chemoembolization (TACE) treatment dataset GSE104580, the response group exhibited lower risk scores than the non-response group (P=0.01), whereas in the 140-sample Sorafenib treatment dataset GSE109211 (P=0.041) and the 17-sample anti-PD-1 treatment dataset GSE202069 (P=0.027), the risk scores were higher in the response group. We also validated the gene expression levels of DCRS and the higher risk scores in the response group of the Guangxi cohort (P=0.034).
Conclusion: A DCRS consisting of 13 genes was established in HCC, facilitating the prediction of patient prognosis and responsiveness to TACE, targeted therapy, and immunotherapy.
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