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Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies

BACKGROUND: Disulfidptosis and the disulfidptosis-related gene SLC7A11 have recently attracted significant attention for their role in tumorigenesis and tumour management. However, its association with adrenocortical carcinoma (ACC) is rarely discussed. METHODS: Differential analysis, Cox regression...

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Autores principales: Liu, Tonghu, Ren, Yilin, Wang, Qixin, Wang, Yu, Li, Zhiyuan, Sun, Weibo, Fan, Dandan, Luan, Yongkun, Gao, Yukui, Yan, Zechen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623781/
https://www.ncbi.nlm.nih.gov/pubmed/37919768
http://dx.doi.org/10.1186/s12935-023-03091-6
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author Liu, Tonghu
Ren, Yilin
Wang, Qixin
Wang, Yu
Li, Zhiyuan
Sun, Weibo
Fan, Dandan
Luan, Yongkun
Gao, Yukui
Yan, Zechen
author_facet Liu, Tonghu
Ren, Yilin
Wang, Qixin
Wang, Yu
Li, Zhiyuan
Sun, Weibo
Fan, Dandan
Luan, Yongkun
Gao, Yukui
Yan, Zechen
author_sort Liu, Tonghu
collection PubMed
description BACKGROUND: Disulfidptosis and the disulfidptosis-related gene SLC7A11 have recently attracted significant attention for their role in tumorigenesis and tumour management. However, its association with adrenocortical carcinoma (ACC) is rarely discussed. METHODS: Differential analysis, Cox regression analysis, and survival analysis were used to screen for the hub gene SLC7A11 in the TCGA and GTEx databases and disulfidptosis-related gene sets. Then, we performed an association analysis between SLC7A11 and clinically relevant factors in ACC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of SLC7A11 and clinically relevant factors. Weighted gene coexpression analysis was used to find genes associated with SLC7A11. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the LinkedOmics database were used to analyse the functions of SLC7A11-associated genes. The CIBERSORT and Xcell algorithms were used to analyse the relationship between SLC7A11 and immune cell infiltration in ACC. The TISIDB database was applied to search for the correlation between SLC7A11 expression and immune chemokines. In addition, we performed a correlation analysis for SLC7A11 expression and tumour mutational burden and immune checkpoint-related genes and assessed drug sensitivity based on SLC7A11 expression. Immunohistochemistry and RT‒qPCR were used to validate the upregulation of SLC7A11 in the ACC. RESULTS: SLC7A11 is highly expressed in multiple urological tumours, including ACC. SLC7A11 expression is strongly associated with clinically relevant factors (M-stage and MYL6 expression) in ACC. SLC7A11 and the constructed nomogram can accurately predict ACC patient outcomes. The functions of SLC7A11 and its closely related genes are tightly associated with the occurrence of disulfidptosis in ACC. SLC7A11 expression was tightly associated with various immune cell infiltration disorders in the ACC tumour microenvironment (TME). It was positively correlated with the expression of immune chemokines (CXCL8, CXCL3, and CCL20) and negatively correlated with the expression of immune chemokines (CXCL17 and CCL14). SLC7A11 expression was positively associated with the expression of immune checkpoint genes (NRP1, TNFSF4, TNFRSF9, and CD276) and tumour mutation burden. The expression level of SLC7A11 in ACC patients is closely associated withcthe drug sensitivity. CONCLUSION: In ACC, high expression of SLC7A11 is associated with migration, invasion, drug sensitivity, immune infiltration disorders, and poor prognosis, and its induction of disulfidptosis is a promising target for the treatment of ACC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03091-6.
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spelling pubmed-106237812023-11-04 Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies Liu, Tonghu Ren, Yilin Wang, Qixin Wang, Yu Li, Zhiyuan Sun, Weibo Fan, Dandan Luan, Yongkun Gao, Yukui Yan, Zechen Cancer Cell Int Research BACKGROUND: Disulfidptosis and the disulfidptosis-related gene SLC7A11 have recently attracted significant attention for their role in tumorigenesis and tumour management. However, its association with adrenocortical carcinoma (ACC) is rarely discussed. METHODS: Differential analysis, Cox regression analysis, and survival analysis were used to screen for the hub gene SLC7A11 in the TCGA and GTEx databases and disulfidptosis-related gene sets. Then, we performed an association analysis between SLC7A11 and clinically relevant factors in ACC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of SLC7A11 and clinically relevant factors. Weighted gene coexpression analysis was used to find genes associated with SLC7A11. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the LinkedOmics database were used to analyse the functions of SLC7A11-associated genes. The CIBERSORT and Xcell algorithms were used to analyse the relationship between SLC7A11 and immune cell infiltration in ACC. The TISIDB database was applied to search for the correlation between SLC7A11 expression and immune chemokines. In addition, we performed a correlation analysis for SLC7A11 expression and tumour mutational burden and immune checkpoint-related genes and assessed drug sensitivity based on SLC7A11 expression. Immunohistochemistry and RT‒qPCR were used to validate the upregulation of SLC7A11 in the ACC. RESULTS: SLC7A11 is highly expressed in multiple urological tumours, including ACC. SLC7A11 expression is strongly associated with clinically relevant factors (M-stage and MYL6 expression) in ACC. SLC7A11 and the constructed nomogram can accurately predict ACC patient outcomes. The functions of SLC7A11 and its closely related genes are tightly associated with the occurrence of disulfidptosis in ACC. SLC7A11 expression was tightly associated with various immune cell infiltration disorders in the ACC tumour microenvironment (TME). It was positively correlated with the expression of immune chemokines (CXCL8, CXCL3, and CCL20) and negatively correlated with the expression of immune chemokines (CXCL17 and CCL14). SLC7A11 expression was positively associated with the expression of immune checkpoint genes (NRP1, TNFSF4, TNFRSF9, and CD276) and tumour mutation burden. The expression level of SLC7A11 in ACC patients is closely associated withcthe drug sensitivity. CONCLUSION: In ACC, high expression of SLC7A11 is associated with migration, invasion, drug sensitivity, immune infiltration disorders, and poor prognosis, and its induction of disulfidptosis is a promising target for the treatment of ACC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03091-6. BioMed Central 2023-11-02 /pmc/articles/PMC10623781/ /pubmed/37919768 http://dx.doi.org/10.1186/s12935-023-03091-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (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, Tonghu
Ren, Yilin
Wang, Qixin
Wang, Yu
Li, Zhiyuan
Sun, Weibo
Fan, Dandan
Luan, Yongkun
Gao, Yukui
Yan, Zechen
Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies
title Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies
title_full Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies
title_fullStr Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies
title_full_unstemmed Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies
title_short Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies
title_sort exploring the role of the disulfidptosis-related gene slc7a11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623781/
https://www.ncbi.nlm.nih.gov/pubmed/37919768
http://dx.doi.org/10.1186/s12935-023-03091-6
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