Research Paper Volume 16, Issue 7 pp 6229—6261
Role of CCR1/5/7 in hepatocellular carcinoma: a study on prognostic evaluation, molecular subtyping, and association with immune infiltration
- 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- 2 Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning 530021, People’s Republic of China
- 3 Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- 4 Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- 5 Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
Received: July 18, 2023 Accepted: February 2, 2024 Published: March 28, 2024
https://doi.org/10.18632/aging.205698How to Cite
Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
This study aims to assess the prognostic value of the C-C motif chemokine receptor (CCR) gene family in hepatocellular carcinoma (HCC) and its relationship with immune infiltration and molecular subtypes of HCC. The evaluation of the GSE14520 dataset and TCGA database confirmed the prognostic significance of CCR. Building upon the correlation between CCR1, CCR5, and CCR7 and favorable prognosis, we further validated the prognostic importance of CCR1, CCR5, and CCR7 in ICGC database and an independent cohort from Guangxi autonomous region. Then, we constructed a risk prognosis model. Additionally, we observed significant positive correlations between CCR1, CCR5, and CCR7 and the infiltration of B cells, T cells, and macrophages in HCC. Subsequently, we conducted CCK assays, Transwell assays, and colony formation assays to evaluate the molecular biological functions of CCR1, CCR5, and CCR7. These experiments further confirmed that upregulation of CCR1, CCR5, and CCR7 can individually inhibit the proliferation, migration, and stemness of HCC cells. By analyzing the relationship between expression levels and tumor mutation frequency, we discovered that patients with high CCR1 expression were more likely to be classified as non-proliferative HCC. Similar conclusions were observed for CCR5 and CCR7. The association of CCR1, CCR5, and CCR7 with the molecular subtypes of HCC suggests that they may serve as intermediary molecules linking immune status and molecular subtypes in HCC. In summary, CCR1, CCR5, and CCR7 have the potential to serve as prognostic biomarkers for HCC and regulate HCC progression by influencing immune cell infiltration.
Abbreviations
CCR: C-C motif chemokine receptor; GSEA: Gene Set Enrichment Analysis; HCC: Hepatocellular Carcinoma; HBV: Hepatitis B Virus; NAFLD: Non-alcohol Fatty Liver Disease; HCV: Hepatitis C virus; DAVID: Database for Annotation, Visualization and Integrated Discovery; GO: Gene Ontology; ROC: Receiver Operating Characteristic Curve; AUC: The Area Under Curve; qPCR: Quantitative polymerase chain reaction; IHC: Immunohistochemistry.