Huang Huasheng, Peng Shayong, Wei Yongguang, Lan Chenlu, Qin Wei, Liao Xiwen, Yang Cheng-Kun, Zhu Guangzhi, Zhou Xin, Peng Tao
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, People's Republic of China.
J Hepatocell Carcinoma. 2024 Sep 17;11:1743-1761. doi: 10.2147/JHC.S481338. eCollection 2024.
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.
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.
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 (=0.003), GSE76427 (=0.005), and GSE14520 (=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 (=0.01), whereas in the 140-sample Sorafenib treatment dataset GSE109211 (=0.041) and the 17-sample anti-PD-1 treatment dataset GSE202069 (=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 (=0.034).
A DCRS consisting of 13 genes was established in HCC, facilitating the prediction of patient prognosis and responsiveness to TACE, targeted therapy, and immunotherapy.
本研究旨在鉴定肝细胞癌（HCC）患者中与树突状细胞（DC）相关的基因，建立DC相关亚型和特征，并将它们与预后和治疗反应相关联。
基于来自TCGA（374个样本）、GSE14520（242个样本）和GSE76427数据集（115个样本）的RNA测序，使用加权基因共表达网络分析（WGCNA）筛选DC相关基因，随后通过TIME方法进行免疫浸润评估。通过无监督聚类鉴定出HCC中的两种DC相关亚型。使用LASSO和Cox回归模型构建预测总生存的DC相关特征（DCRS），并在三个数据集中进行验证。此外，在DCRS风险组中探索基因突变特征、免疫浸润水平和治疗敏感性。使用Wilcoxon检验在广西队列中13例接受联合靶向治疗和免疫治疗的HCC患者的转录组中验证DCRS基因的表达水平和风险评分。
构建了一个由13个与DC相关的基因组成的特征，低DCRS风险组的优越预后一致性在TCGA（=0.003）、GSE76427（=0.005）和GSE14520（=0.047）数据集中得到验证。此外，在147个样本的经动脉化疗栓塞（TACE）治疗数据集GSE104580中，反应组的风险评分低于无反应组（=0.01），而在140个样本的索拉非尼治疗数据集GSE109211（=0.041）和17个样本的抗PD-1治疗数据集GSE202069（=0.027）中，反应组的风险评分更高。我们还在广西队列的反应组中验证了DCRS的基因表达水平和更高风险评分（=0.034）。
在HCC中建立了一个由13个基因组成的DCRS，有助于预测患者预后以及对TACE、靶向治疗和免疫治疗的反应性。
