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Comprehensive analysis of scRNA-Seq and bulk RNA-Seq data reveals dynamic changes in tumor-associated neutrophils in the tumor microenvironment of hepatocellular carcinoma and leads to the establishment of a neutrophil-related prognostic model

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Background

Analysis of hepatocellular carcinoma (HCC) single-cell sequencing data was conducted to explore the role of tumor-associated neutrophils in the tumor microenvironment.

Methods

Analysis of single-cell sequencing data from 12 HCC tumor cores and five HCC paracancerous tissues identified cellular subpopulations and cellular marker genes. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to establish and validate prognostic models. xCELL, TIMER, QUANTISEQ, CIBERSORT, and CIBERSORT-abs analyses were performed to explore immune cell infiltration. Finally, the pattern of tumor-associated neutrophil roles in tumor microenvironmental components was explored.

Results

A total of 271 marker genes for tumor-associated neutrophils were identified based on single-cell sequencing data. Prognostic models incorporating eight genes were established based on TCGA data. Immune cell infiltration differed between the high- and low-risk groups. The low-risk group benefited more from immunotherapy. Single-cell analysis indicated that tumor-associated neutrophils were able to influence macrophage, NK cell, and T-cell functions through the IL16, IFN-II, and SPP1 signaling pathways.

Conclusion

Tumor-associated neutrophils regulate immune functions by influencing macrophages and NK cells. Models incorporating tumor-associated neutrophil-related genes can be used to predict patient prognosis and immunotherapy responses.

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Data availability

Publicly available datasets were analyzed in this study.

Abbreviations

GEO:

Gene expression omnibus

GSEA:

Gene set enrichment analysis

HCC:

Hepatocellular carcinoma

KEGG:

Kyoto encyclopedia of genes and genomes

LASSO:

Least absolute shrinkage and selection operator

RT-qPCR:

Real-time quantitative PCR

ROC:

Receiver operating characteristic

ssGSEA:

Single-sample GSEA

TCGA:

The cancer genome atlas program

UMAP:

Uniform manifold approximation and projection

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Acknowledgements

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Funding

This study was funded by the Hubei Provincial Fund Committee (2022CFB122).

Author information

Author notes

  1. Dashuai Yang, Yu Zhou and Yanbing Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, China

    Dashuai Yang, Yu Zhou, Yanbing Zhang, Jie Shen, Bin Yu, Kailiang Zhao & Youming Ding

  2. Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College in Huazhong University of Science and Technology, Wuhan, 430060, Hubei, China

    Yang Su

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  1. Dashuai Yang
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Contributions

DY contributed to the conceptualization, JS, BY, and YS were involved in data curation, Yu Zhou and Yanbing Zhang contributed to the formal analysis, DY and Yu Zhou were involved in writing—original draft, and YD and KZ contributed to writing—review and editing.

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Correspondence to Kailiang Zhao or Youming Ding.

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Ethical approval

This study was approved by the Ethics Committee of Renmin Hospital of Wuhan University. Written informed consent was obtained from all patients to participate in the study.

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Yang, D., Zhou, Y., Zhang, Y. et al. Comprehensive analysis of scRNA-Seq and bulk RNA-Seq data reveals dynamic changes in tumor-associated neutrophils in the tumor microenvironment of hepatocellular carcinoma and leads to the establishment of a neutrophil-related prognostic model. Cancer Immunol Immunother 72, 4323–4335 (2023). https://doi.org/10.1007/s00262-023-03567-4

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