4.8 Article

The role of cuproptosis-related gene in the classification and prognosis of melanoma

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.986214

Keywords

melanoma; subtype; machine learning; prognostic model; metastasis model; cuproptosis

Categories

Funding

  1. National Key R&D Program of China
  2. National Natural Science Foundation of China
  3. Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University
  4. Postgraduate Research and Innovation Project of Central South University
  5. [2020YFC2005000]
  6. [81802668]
  7. [82172832]
  8. [YX202108]
  9. [2020zzts892]

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The study found that cuproptosis-related genes in melanoma are associated with metastasis and prognosis. By establishing molecular subtypes and gene subtypes, constructing a prognostic model, screening out 98 drugs, and establishing a metastasis model.
BackgroundMelanoma, as one of the most aggressive and malignant cancers, ranks first in the lethality rate of skin cancers. Cuproptosis has been shown to paly a role in tumorigenesis, However, the role of cuproptosis in melanoma metastasis are not clear. Studying the correlation beteen the molecular subtypes of cuproptosis-related genes (CRGs) and metastasis of melanoma may provide some guidance for the prognosis of melanoma. MethodsWe collected 1085 melanoma samples in The Cancer Genome Atlas(TCGA) and Gene Expression Omnibus(GEO) databases, constructed CRGs molecular subtypes and gene subtypes according to clinical characteristics, and investigated the role of CRGs in melanoma metastasis. We randomly divide the samples into train set and validation set according to the ratio of 1:1. A prognostic model was constructed using data from the train set and then validated on the validation set. We performed tumor microenvironment analysis and drug sensitivity analyses for high and low risk groups based on the outcome of the prognostic model risk score. Finally, we established a metastatic model of melanoma. ResultsAccording to the expression levels of 12 cuproptosis-related genes, we obtained three subtypes of A(1), B-1, and C-1. Among them, C-1 subtype had the best survival outcome. Based on the differentially expressed genes shared by A(1), B-1, and C-1 genotypes, we obtained the results of three gene subtypes of A(2), B-2, and C-2. Among them, the B-2 group had the best survival outcome. Then, we constructed a prognostic model consisting of 6 key variable genes, which could more accurately predict the 1-, 3-, and 5-year overall survival rates of melanoma patients. Besides, 98 drugs were screened out. Finally, we explored the role of cuproptosis-related genes in melanoma metastasis and established a metastasis model using seven key genes. ConclusionsIn conclusion, CRGs play a role in the metastasis and prognosis of melanoma, and also provide new insights into the underlying pathogenesis of melanoma.

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