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Identification of immunophenotypes in esophageal squamous cell carcinoma based on immune gene sets

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Abstract

Purpose

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high heterogeneity. Research on molecular mechanisms involved in the process of tumor origination and progression is extremely limited to investigating mechanisms of molecular typing for ESCC.

Methods

After comprehensively analyzing the gene expression profiles in The Cancer Genome Atlas and Gene Expression Omnibus databases, we identified four immunotypes of ESCC (referred to as C1–C4) based on the gene sets of 28 immune cell subpopulations. The discrepancies in prognostic value, clinical features, drug sensitivity, and tumor components between the immunotypes were individually analyzed.

Results

The ranking of immune infiltration is C1 > C4 > C3 > C2. These subtypes are characterized by high and low expression of immune checkpoint proteins, enrichment and insufficiency of immune-related pathways, and differential distribution of immune cell subgroups. Poorer survival was observed in the C1 subtype, which we hypothesized could be caused by an immunosuppressive cell population. Fortunately, C1’s susceptibility to anti-PD-1 therapy offers hope for patients with poor prognosis in advanced stages. On the other hand, C4 is sensitive to docetaxel, which may offer novel treatment strategies for ESCC in the future. It is worth noting that immunophenotyping is tightly bound to the abundance of stromal components and stem cells, which could explain the tumor immune escape to some extent. Ultimately, determination of hub genes based on the C1 subtypes provides a reference for the discovery of immunotarget drugs against ESCC.

Conclusion

The identification of immunophenotypes in our study provides new therapeutic strategies for patients with ESCC.

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Notes

  1. https://cancergenome.nih.gov/.

  2. http://www.ncbi.nlm.nih.gov/geo.

  3. http://asia.ensembl.org/index.html.

  4. https://www.gencodegenes.org/.

  5. https://cloud.genepattern.org/.

  6. https://www.cancerrxgene.org/.

  7. https://www.immport.org/.

  8. https://cn.string-db.org/.

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Acknowledgements

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China (71964021, 81960430), the Fundamental Research Funds for the Central Universities (lzujbky-2021-ct17, lzujbky-2021-kb35), and the Foundation of The First Hospital of Lanzhou University, China (ldyyyn2019-74, ldyyyn2018-38, ldyyyn2018-54).

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Authors and Affiliations

  1. The First Clinical Medical College, Lanzhou University, Lanzhou, China

    Danlei Song, Yuping Hu, Yueting Sun & Yongning Zhou

  2. Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China

    Danlei Song, Yueting Sun, Min Liu, Qian Ren, Zenan Hu, Qinghong Guo, Yuping Wang & Yongning Zhou

  3. The First Department of Hepatobiliary and Pancreatic Surgery, Cangzhou Central Hospital, Cangzhou, China

    Yongjian Wei

  4. Hospital of Reproductive Medicine, The First Hospital of Lanzhou University, Lanzhou, China

    Yuping Hu

Authors
  1. Danlei Song
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  2. Yongjian Wei
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  3. Yuping Hu
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  4. Yueting Sun
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  5. Min Liu
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  7. Zenan Hu
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  8. Qinghong Guo
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  9. Yuping Wang
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  10. Yongning Zhou
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Contributions

D.L. Song: visualization, software, data curation, writing—original draft; Y.J. Wei: visualization, software; Y.P. Hu: writing—original draft. Y.T. Sun: writing—review and editing; M. Liu: writing—review and editing; Q. Ren: funding acquisition; Z.N. Hu: writing—review and editing; Q.H. Guo: funding acquisition; Y.P. Wang: data curation, writing—review and editing; Y.N. Zhou: funding acquisition, methodology, writing—review and editing.

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Correspondence to Yongning Zhou.

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Song, D., Wei, Y., Hu, Y. et al. Identification of immunophenotypes in esophageal squamous cell carcinoma based on immune gene sets. Clin Transl Oncol 24, 1100–1114 (2022). https://doi.org/10.1007/s12094-021-02749-9

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  • DOI: https://doi.org/10.1007/s12094-021-02749-9

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