Efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is a highly lethal liver cancer with late diagnosis; therefore, the identification of new early biomarkers could help reduce mortality. Efferocytosis, a process in which one cell engulfs another cell, including macrophages, dendritic cells, NK cells, etc.,...

Full description

Bibliographic Details
Main Authors: Ke Xu, Yu Liu, Huiyan Luo, Tengfei Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1218244/full
_version_ 1797805738151641088
author Ke Xu
Yu Liu
Huiyan Luo
Tengfei Wang
author_facet Ke Xu
Yu Liu
Huiyan Luo
Tengfei Wang
author_sort Ke Xu
collection DOAJ
description Background: Hepatocellular carcinoma (HCC) is a highly lethal liver cancer with late diagnosis; therefore, the identification of new early biomarkers could help reduce mortality. Efferocytosis, a process in which one cell engulfs another cell, including macrophages, dendritic cells, NK cells, etc., plays a complex role in tumorigenesis, sometimes promoting and sometimes inhibiting tumor development. However, the role of efferocytosis-related genes (ERGs) in HCC progression has been poorly studied, and their regulatory effects in HCC immunotherapy and drug targeting have not been reported.Methods: We downloaded efferocytosis-related genes from the Genecards database and screened for ERGs that showed significant expression changes between HCC and normal tissues and were associated with HCC prognosis. Machine learning algorithms were used to study prognostic gene features. CIBERSORT and pRRophetic R packages were used to evaluate the immune environment of HCC subtypes and predict treatment response. CCK-8 experiments conducted on HCC cells were used to assess the reliability of drug sensitivity prediction.Results: We constructed a prognostic prediction model composed of six genes, and the ROC curve showed good predictive accuracy of the risk model. In addition, two ERG-related subgroups in HCC showed significant differences in tumor immune landscape, immune response, and prognostic stratification. The CCK-8 experiment conducted on HCC cells confirmed the reliability of drug sensitivity prediction.Conclusion: Our study emphasizes the importance of efferocytosis in HCC progression. The risk model based on efferocytosis-related genes developed in our study provides a novel precision medicine approach for HCC patients, allowing clinicians to customize treatment plans based on unique patient characteristics. The results of our investigation carry noteworthy implications for the development of individualized treatment approaches involving immunotherapy and chemotherapy, thereby potentially facilitating the realization of personalized and more efficacious therapeutic interventions for HCC.
first_indexed 2024-03-13T05:56:35Z
format Article
id doaj.art-144b63ba69bc4d9bbf26f1da24e2f033
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-03-13T05:56:35Z
publishDate 2023-06-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-144b63ba69bc4d9bbf26f1da24e2f0332023-06-13T04:41:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-06-011410.3389/fphar.2023.12182441218244Efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinomaKe Xu0Yu Liu1Huiyan Luo2Tengfei Wang3Department of Oncology, Chongqing General Hospital, Chongqing, ChinaDepartment of Oncology, Chongqing General Hospital, Chongqing, ChinaDepartment of Oncology, Chongqing General Hospital, Chongqing, ChinaDepartment of Equipment, Bishan Hospital of Chongqing, Chongqing, ChinaBackground: Hepatocellular carcinoma (HCC) is a highly lethal liver cancer with late diagnosis; therefore, the identification of new early biomarkers could help reduce mortality. Efferocytosis, a process in which one cell engulfs another cell, including macrophages, dendritic cells, NK cells, etc., plays a complex role in tumorigenesis, sometimes promoting and sometimes inhibiting tumor development. However, the role of efferocytosis-related genes (ERGs) in HCC progression has been poorly studied, and their regulatory effects in HCC immunotherapy and drug targeting have not been reported.Methods: We downloaded efferocytosis-related genes from the Genecards database and screened for ERGs that showed significant expression changes between HCC and normal tissues and were associated with HCC prognosis. Machine learning algorithms were used to study prognostic gene features. CIBERSORT and pRRophetic R packages were used to evaluate the immune environment of HCC subtypes and predict treatment response. CCK-8 experiments conducted on HCC cells were used to assess the reliability of drug sensitivity prediction.Results: We constructed a prognostic prediction model composed of six genes, and the ROC curve showed good predictive accuracy of the risk model. In addition, two ERG-related subgroups in HCC showed significant differences in tumor immune landscape, immune response, and prognostic stratification. The CCK-8 experiment conducted on HCC cells confirmed the reliability of drug sensitivity prediction.Conclusion: Our study emphasizes the importance of efferocytosis in HCC progression. The risk model based on efferocytosis-related genes developed in our study provides a novel precision medicine approach for HCC patients, allowing clinicians to customize treatment plans based on unique patient characteristics. The results of our investigation carry noteworthy implications for the development of individualized treatment approaches involving immunotherapy and chemotherapy, thereby potentially facilitating the realization of personalized and more efficacious therapeutic interventions for HCC.https://www.frontiersin.org/articles/10.3389/fphar.2023.1218244/fullHCCefferocytosisimmunetherapybiomarker
spellingShingle Ke Xu
Yu Liu
Huiyan Luo
Tengfei Wang
Efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinoma
Frontiers in Pharmacology
HCC
efferocytosis
immune
therapy
biomarker
title Efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinoma
title_full Efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinoma
title_fullStr Efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinoma
title_full_unstemmed Efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinoma
title_short Efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinoma
title_sort efferocytosis signatures as prognostic markers for revealing immune landscape and predicting immunotherapy response in hepatocellular carcinoma
topic HCC
efferocytosis
immune
therapy
biomarker
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1218244/full
work_keys_str_mv AT kexu efferocytosissignaturesasprognosticmarkersforrevealingimmunelandscapeandpredictingimmunotherapyresponseinhepatocellularcarcinoma
AT yuliu efferocytosissignaturesasprognosticmarkersforrevealingimmunelandscapeandpredictingimmunotherapyresponseinhepatocellularcarcinoma
AT huiyanluo efferocytosissignaturesasprognosticmarkersforrevealingimmunelandscapeandpredictingimmunotherapyresponseinhepatocellularcarcinoma
AT tengfeiwang efferocytosissignaturesasprognosticmarkersforrevealingimmunelandscapeandpredictingimmunotherapyresponseinhepatocellularcarcinoma