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Identification of ferroptosis genes in immune infiltration and prognosis in thyroid papillary carcinoma using network analysis5.21 MB
Published VersionCC BY V4.0, Open Access
Journal article
Identification of ferroptosis genes in immune infiltration and prognosis in thyroid papillary carcinoma using network analysis
BMC Genomics, Vol.22(1), pp.1-16
2021
Abstract
Background:
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. While many patients survive, a portion of PTC cases display high aggressiveness and even develop into refractory differentiated thyroid carcinoma. This may be alleviated by developing a novel model to predict the risk of recurrence. Ferroptosis is an iron-dependent form of regulated cell death (RCD) driven by lethal accumulation of lipid peroxides, is regulated by a set of genes and shows a variety of metabolic changes. To elucidate whether ferroptosis occurs in PTC, we analyse the gene expression profiles of the disease and established a new model for the correlation.
Methods:
The thyroid carcinoma (THCA) datasets were downloaded from The Cancer Genome Atlas (TCGA), UCSC Xena and MisgDB, and included 502 tumour samples and 56 normal samples. A total of 60 ferroptosis related genes were summarised from MisgDB database. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) were used to analyse pathways potentially involving PTC subtypes. Single sample GSEA (ssGSEA) algorithm was used to analyse the proportion of 28 types of immune cells in the tumour immune infiltration microenvironment in THCA and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells. Spearman correlation analysis was performed on the ferroptosis gene expression and the correlation between immune infiltrating cells proportion. We established the WGCNA to identify genes modules that are highly correlated with the microenvironment of immune invasion. DEseq2 algorithm was further used for differential analysis of sequencing data to analyse the functions and pathways potentially involving hub genes. GO and KEGG enrichment analysis was performed using Clusterprofiler to explore the clinical efficacy of hub genes. Univariate Cox analysis was performed for hub genes combined with clinical prognostic data, and the results was included for lasso regression and constructed the risk regression model. ROC curve and survival curve were used for
evaluating the model. Univariate Cox analysis and multivariate Cox analysis were performed in combination with the clinical data of THCA and the risk score value, the clinical efficacy of the model was further evaluated.
Results:
We identify two subtypes in PTC based on the expression of ferroptosis related genes, with the proportion of cluster 1 significantly higher than cluster 2 in ferroptosis signature genes that are positively associated. The mutations of Braf and Nras are detected as the major mutations of cluster 1 and 2, respectively. Subsequent analyses of TME immune cells infiltration indicated cluster 1 is remarkably richer than cluster 2. The risk score of THCA is in good performance evaluated by ROC curve and survival curve, in conjunction with univariate Cox
analysis and multivariate Cox analysis results based on the clinical data shows that the risk score of the proposed model could be used as an independent prognostic indicator to predict the prognosis of patients with papillary thyroid cancer.
Conclusions:
Our study finds seven crucial genes, including Ac008063.2, Apoe, Bcl3, Acap3, Alox5ap, Atxn2l and B2m, and regulation of apoptosis by parathyroid hormone-related proteins significantly associated with ferroptosis and immune cells in PTC, and we construct the risk score model which can be used as an independent prognostic index to predict the prognosis of patients with PTC.
Details
- Title
- Identification of ferroptosis genes in immune infiltration and prognosis in thyroid papillary carcinoma using network analysis
- Authors
- Ruoting Lin (Author) - Guangdong Pharmaceutical UniversityConor E Fogarty (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyBowei Ma (Author) - First Affiliated Hospital of Guangzhou University of Chinese MedicineHejie Li (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyGuoying Ni (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyXiaosong Liu (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyJianwei Yuan (Author) - Guangdong Pharmaceutical UniversityTianfang Wang (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
- Publication details
- BMC Genomics, Vol.22(1), pp.1-16
- Publisher
- BioMed Central Ltd.
- Date published
- 2021
- DOI
- 10.1186/s12864-021-07895-6
- ISSN
- 1471-2164
- Copyright note
- © The Author(s). 2021 Open Access This 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/. The Creative Commons Public Domain Dedication waiver (http://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.
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99578808902621
- Output Type
- Journal article
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