Cargando…

Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma

BACKGROUND: Cutaneous Melanoma (CM) is a malignant disease with increasing incidence and high mortality. Ferroptosis is a new kind of cell death and related to tumor blood and lymphatic metastasis. This study aims at using bioinformatics technology to construct a prognostic signature and identify fe...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Changjiang, Liu, Yuhang, Yu, Yifeng, Zhao, Yong, Yu, Aixi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886785/
https://www.ncbi.nlm.nih.gov/pubmed/35232428
http://dx.doi.org/10.1186/s12920-022-01194-z
_version_ 1784660754831507456
author Liu, Changjiang
Liu, Yuhang
Yu, Yifeng
Zhao, Yong
Yu, Aixi
author_facet Liu, Changjiang
Liu, Yuhang
Yu, Yifeng
Zhao, Yong
Yu, Aixi
author_sort Liu, Changjiang
collection PubMed
description BACKGROUND: Cutaneous Melanoma (CM) is a malignant disease with increasing incidence and high mortality. Ferroptosis is a new kind of cell death and related to tumor blood and lymphatic metastasis. This study aims at using bioinformatics technology to construct a prognostic signature and identify ferroptosis-related biomarkers to improve the prognosis and treatment of cutaneous melanoma. METHODS: We used bioinformatics tools to analyze RNA sequencing expression data with clinical information from multiple databases, utilized varieties of statistical methods to construct a ferroptosis-related prognostic signature of cutaneous melanoma and screened out specific genes with independent prognostic ability. RESULTS: We obtained 22 ferroptosis-related (P < 0.05) prognostic DEGs in the uniCox regression analysis, among which 10 high-expressed genes (ATG5, CHAC1, FANCD2, FBXL5, HMOX2, HSPB1, NQO1, PEBP1, PRNP, SLC3A2) were screened out by LASSO regression analysis to establish a predictive model. Meanwhile, the ferroptosis-related signature and the nomogram we drew performed an excellent performance based on Kaplan–Meier (K–M), Receiver operating characteristic (ROC) and calibration curves. Univariate and multivariable cox analyses displayed that our model was greater than other prognostic features. GO and KEGG analyses revealed that 10-biomarker signature was mainly related to epidermis differentiation and immunity. ssGSEA analysis indicated that the immune status between the two risk groups was highly different. Besides, we found that two genes (CP, ZEB1) had independent prognostic ability and can be applied for drug research. Both genes were highly related to immunity. GSEA illustrated that ZEB1 may be involved in cellular functions such as proliferation, apoptosis, and migration, while CP was closely connected to immune cell related functions. CONCLUSION: The present study suggested a 10-biomarker signature can be clinically used to predict the prognosis of cutaneous melanoma, which was better than conventional factors. CP and ZEB1 were independent prognostic genes and can be applied to guide treatment. In addition, ZEB1 mutation was highly related to overall survival in cutaneous melanoma, while CP may be associated with tumor progression. Our study comprehensively analyzed the relationship between iron metabolism, ferroptosis-related genes, and the prognosis of cutaneous melanoma, provided new insight for molecular mechanisms and treatment of ferroptosis and cutaneous melanoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01194-z.
format Online
Article
Text
id pubmed-8886785
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-88867852022-03-17 Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma Liu, Changjiang Liu, Yuhang Yu, Yifeng Zhao, Yong Yu, Aixi BMC Med Genomics Research BACKGROUND: Cutaneous Melanoma (CM) is a malignant disease with increasing incidence and high mortality. Ferroptosis is a new kind of cell death and related to tumor blood and lymphatic metastasis. This study aims at using bioinformatics technology to construct a prognostic signature and identify ferroptosis-related biomarkers to improve the prognosis and treatment of cutaneous melanoma. METHODS: We used bioinformatics tools to analyze RNA sequencing expression data with clinical information from multiple databases, utilized varieties of statistical methods to construct a ferroptosis-related prognostic signature of cutaneous melanoma and screened out specific genes with independent prognostic ability. RESULTS: We obtained 22 ferroptosis-related (P < 0.05) prognostic DEGs in the uniCox regression analysis, among which 10 high-expressed genes (ATG5, CHAC1, FANCD2, FBXL5, HMOX2, HSPB1, NQO1, PEBP1, PRNP, SLC3A2) were screened out by LASSO regression analysis to establish a predictive model. Meanwhile, the ferroptosis-related signature and the nomogram we drew performed an excellent performance based on Kaplan–Meier (K–M), Receiver operating characteristic (ROC) and calibration curves. Univariate and multivariable cox analyses displayed that our model was greater than other prognostic features. GO and KEGG analyses revealed that 10-biomarker signature was mainly related to epidermis differentiation and immunity. ssGSEA analysis indicated that the immune status between the two risk groups was highly different. Besides, we found that two genes (CP, ZEB1) had independent prognostic ability and can be applied for drug research. Both genes were highly related to immunity. GSEA illustrated that ZEB1 may be involved in cellular functions such as proliferation, apoptosis, and migration, while CP was closely connected to immune cell related functions. CONCLUSION: The present study suggested a 10-biomarker signature can be clinically used to predict the prognosis of cutaneous melanoma, which was better than conventional factors. CP and ZEB1 were independent prognostic genes and can be applied to guide treatment. In addition, ZEB1 mutation was highly related to overall survival in cutaneous melanoma, while CP may be associated with tumor progression. Our study comprehensively analyzed the relationship between iron metabolism, ferroptosis-related genes, and the prognosis of cutaneous melanoma, provided new insight for molecular mechanisms and treatment of ferroptosis and cutaneous melanoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01194-z. BioMed Central 2022-03-01 /pmc/articles/PMC8886785/ /pubmed/35232428 http://dx.doi.org/10.1186/s12920-022-01194-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Changjiang
Liu, Yuhang
Yu, Yifeng
Zhao, Yong
Yu, Aixi
Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma
title Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma
title_full Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma
title_fullStr Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma
title_full_unstemmed Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma
title_short Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma
title_sort comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886785/
https://www.ncbi.nlm.nih.gov/pubmed/35232428
http://dx.doi.org/10.1186/s12920-022-01194-z
work_keys_str_mv AT liuchangjiang comprehensiveanalysisofferroptosisrelatedgenesandprognosisofcutaneousmelanoma
AT liuyuhang comprehensiveanalysisofferroptosisrelatedgenesandprognosisofcutaneousmelanoma
AT yuyifeng comprehensiveanalysisofferroptosisrelatedgenesandprognosisofcutaneousmelanoma
AT zhaoyong comprehensiveanalysisofferroptosisrelatedgenesandprognosisofcutaneousmelanoma
AT yuaixi comprehensiveanalysisofferroptosisrelatedgenesandprognosisofcutaneousmelanoma