Huasheng Huang,1– 3 Shayong Peng,1– 3 Yongguang Wei,1– 3 Chenlu Lan,1– 3 Wei Qin,1– 3 Xiwen Liao,1– 3 Cheng-Kun Yang,1– 3 Guangzhi Zhu,1– 3 Xin Zhou,1– 3 Tao Peng1– 3 

1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, People’s Republic of China; 3Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China

Correspondence: Tao Peng; Xin Zhou, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6#, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86-771-5356528, Fax +86-771-5350031, Email pengtaogmu@163.com; zhouxin_gxmu@163.com

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.

Keywords: hepatocellular carcinoma, dendritic cells, prognosis, immunotherapy, targeted therapy