Dendritic Cell-Related Gene Signatures in Hepatocellular Carcinoma: An Analysis for Prognosis and Therapy Efficacy Evaluation

Huasheng Huang; Shayong Peng; Yongguang Wei; Chenlu Lan; Wei Qin; Xiwen Liao; Cheng-Kun Yang; Guangzhi Zhu; Xin Zhou; Tao Peng

doi:10.2147/JHC.S481338

Dendritic Cell-Related Gene Signatures in Hepatocellular Carcinoma: An Analysis for Prognosis and Therapy Efficacy Evaluation

J Hepatocell Carcinoma. 2024 Sep 17:11:1743-1761. doi: 10.2147/JHC.S481338. eCollection 2024.

Authors

Huasheng Huang^{1

2

3}, Shayong Peng^{1

2

3}, Yongguang Wei^{1

2

3}, Chenlu Lan^{1

2

3}, Wei Qin^{1

2

3}, Xiwen Liao^{1

2

3}, Cheng-Kun Yang^{1

2

3}, Guangzhi Zhu^{1

2

3}, Xin Zhou^{1

2

3}, Tao Peng^{1

2

3}

Affiliations

¹ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
² Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, People's Republic of China.
³ Key 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.

Abstract

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: dendritic cells; hepatocellular carcinoma; immunotherapy; prognosis; targeted therapy.

Grants and funding

This work was supported in part by the Guangxi Research Basic Ability Improvement Project for Young and Middle-aged Teachers (2024KY0128) and the National Funded Postdoctoral Researcher Program (GZC20230583). The research was supported by the National Natural Science Foundation (82060434) and the Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation (No.2023JJD140130). Besides, this research was partly supported by professor Tao Peng with Key Laboratory of early Prevention & Treatment for regional High Frequency Tumor (Guangxi Medical University)-Ministry of Education (grant nos. GKE2018-01, GKE2019-11, GKE-ZZ202009 and GKEZZ202109), Key R&D Plan of Qingxiu District, Nanning (NO.2020056) and Self-funded Scientific Research Project of Health Commission in Guangxi Zhuang Autonomous Region (Z20210977). The Self-raised Scientific Research Fund of the Health and Family Planning Commission of the Guangxi Zhuang Autonomous Region (grant no.Z-A20230458).