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Identification of immune-related genes with prognostic significance in the microenvironment of cutaneous melanoma

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Abstract

Cutaneous melanoma is one of the most aggressive cancers characterized by increasing incidence and mortality. In recent years, the emergence of immunotherapy has greatly raised the survival rate of patients suffering from cutaneous melanoma, yet some sufferers remain to have poor outcomes after treatment mainly due to the tumor microenvironment (TME). In this study, cutaneous melanoma–associated TME was systematically analyzed using the ESTIMATE algorithm based on the gene transcriptome data obtained from the TCGA database. Totally, 471 patients were included and 553 TME-related genes were screened. Afterwards, a 3-gene signature–based model (CLEC4A, GBP4, KIR2DL4) was constructed via univariate Cox, LASSO, and multivariate Cox regression analyses. To validate the validity of this model, ROC analysis was conducted, and the model was further validated to be an independent prognostic biomarker through univariate and multivariate regression analyses. Finally, the three genes in the model were studied by GSEA and GSVA for their biological significance. We found that the three genes could promote cancer immune response predominantly through affecting immune-related pathways such as antigen processing and presentation, and they may help tumor cells in escaping from surveillance of the immune system when their expression levels were decreased. Additionally, we as well discovered that the expression of the three genes was significantly and positively correlated with the infiltration of related immune cells, but negatively associated with tumor purity. Overall, this study comprehensively analyzed the TME of cutaneous melanoma, identified related biomarkers, and discovered their association with immune system.

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The data and materials in the current study are available from the corresponding author on reasonable request.

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Author notes

  1. Yan Qu and Shuqing Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Yantai Yuhuangding Hospital, No. 20, Yuhuangding East Road, Zhifu District, Yantai City, 264099, China

    Yan Qu & Xien Feng

  2. Department of Dermatology, Yantai Yuhuangding Hospital Laishan Branch, Yantai, China

    Shuqing Zhang

  3. Department of Dermatology, Zoucheng People’s Hospital, Zoucheng, China

    Yan Zhang

  4. Department of Dermatology, Dongying District People’s Hospital of Dongying City, No. 333 Jinan Road, Dongying District, Dongying, 257000, China

    Fengjuan Wang

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QY and SQ both contributed to the work, including conception and design, article drafting, and revising. ZY, XE, and FJ are the guarantor for the article who accepts full responsibility for the work.

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Correspondence to Yan Qu or Fengjuan Wang.

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ESM 1

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ESM 3

Raw clinical data downloaded from TCGA database (XLSX 29.2 kb)

ESM 4

Stromal, immune and ESTIMATE scores calculated by ESTIMATE algorithm (XLSX 38.5 kb)

ESM 5

The genes significantly correlated with overall survival in patients (XLSX 37.2 kb)

ESM 6

Clinical significance of the risk model (XLSX 12 kb)

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Qu, Y., Zhang, S., Zhang, Y. et al. Identification of immune-related genes with prognostic significance in the microenvironment of cutaneous melanoma. Virchows Arch 478, 943–959 (2021). https://doi.org/10.1007/s00428-020-02948-9

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