The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer.

The primary drawbacks of current cancer therapies are lower selectivity for cancer cells, more side effects, and obscure resistance mechanisms. Novel approaches to overcome these drawbacks comprise the utilization of ionophores and metalliferous chelators to change the concentration of trace metal e...

Full description

Saved in:
Bibliographic Details
Main Authors: Jianpeng Zhou, Chuanlei Wang, Yao Zhi, Jia Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0324389
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849427402491428864
author Jianpeng Zhou
Chuanlei Wang
Yao Zhi
Jia Li
author_facet Jianpeng Zhou
Chuanlei Wang
Yao Zhi
Jia Li
author_sort Jianpeng Zhou
collection DOAJ
description The primary drawbacks of current cancer therapies are lower selectivity for cancer cells, more side effects, and obscure resistance mechanisms. Novel approaches to overcome these drawbacks comprise the utilization of ionophores and metalliferous chelators to change the concentration of trace metal elements in cancer cells. As the concept of cuproptosis emerged, it might be a novel strategy to enhance the curative effects for resistant cancer cells potentially. FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, and SLC31A1 are the major regulators of cuproptosis. However, the expression landscape and clinical roles of these regulators remain to be addressed. This study explored the expression pattern and clinical role of these cuproptosis-related genes in pan-cancer by evaluating the association of tumor mutation burden (TMB), immune-related scores, cells in tumor microenvironment, and drug sensibility. The results displayed that the expressions of cuproptosis-related genes were significantly different in various cancer types, all cuproptosis-related gene upregulates significantly in LAML, ALL, PAAD, GBM, GBMLGG, LGG, and all significantly downregulated in cancers KIPP, WT, KIPAN, KIRC. Furthermore, the higher the level of cuproptosis-related genes expressed, the higher the survival in patients suffering from KIRC, and KIPAN increased. In addition, the expression of cuproptosis-related genes was negatively associated with immune-related scores, while SLC31A1 had a positive association with StromalScore, ImmuneScore, and EstimateScore in LAML. Importantly, the expression of cuproptosis-related genes was positively correlated with common lymphoid progenitor (CLP) cells and Th2 cells, but negatively associated with NKT cells or Th1 cells. These findings suggest that cuproptosis-related genes are dysregulated across cancer types, hold prognostic value, and may be involved in modulating the tumor immune microenvironment.
format Article
id doaj-art-0d401b561e6644f893c342f06fd724f7
institution Kabale University
issn 1932-6203
language English
publishDate 2025-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-0d401b561e6644f893c342f06fd724f72025-08-20T03:29:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e032438910.1371/journal.pone.0324389The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer.Jianpeng ZhouChuanlei WangYao ZhiJia LiThe primary drawbacks of current cancer therapies are lower selectivity for cancer cells, more side effects, and obscure resistance mechanisms. Novel approaches to overcome these drawbacks comprise the utilization of ionophores and metalliferous chelators to change the concentration of trace metal elements in cancer cells. As the concept of cuproptosis emerged, it might be a novel strategy to enhance the curative effects for resistant cancer cells potentially. FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, and SLC31A1 are the major regulators of cuproptosis. However, the expression landscape and clinical roles of these regulators remain to be addressed. This study explored the expression pattern and clinical role of these cuproptosis-related genes in pan-cancer by evaluating the association of tumor mutation burden (TMB), immune-related scores, cells in tumor microenvironment, and drug sensibility. The results displayed that the expressions of cuproptosis-related genes were significantly different in various cancer types, all cuproptosis-related gene upregulates significantly in LAML, ALL, PAAD, GBM, GBMLGG, LGG, and all significantly downregulated in cancers KIPP, WT, KIPAN, KIRC. Furthermore, the higher the level of cuproptosis-related genes expressed, the higher the survival in patients suffering from KIRC, and KIPAN increased. In addition, the expression of cuproptosis-related genes was negatively associated with immune-related scores, while SLC31A1 had a positive association with StromalScore, ImmuneScore, and EstimateScore in LAML. Importantly, the expression of cuproptosis-related genes was positively correlated with common lymphoid progenitor (CLP) cells and Th2 cells, but negatively associated with NKT cells or Th1 cells. These findings suggest that cuproptosis-related genes are dysregulated across cancer types, hold prognostic value, and may be involved in modulating the tumor immune microenvironment.https://doi.org/10.1371/journal.pone.0324389
spellingShingle Jianpeng Zhou
Chuanlei Wang
Yao Zhi
Jia Li
The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer.
PLoS ONE
title The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer.
title_full The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer.
title_fullStr The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer.
title_full_unstemmed The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer.
title_short The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer.
title_sort potential role of cuproptosis related genes for therapy and immunoregulation in pan cancer
url https://doi.org/10.1371/journal.pone.0324389
work_keys_str_mv AT jianpengzhou thepotentialroleofcuproptosisrelatedgenesfortherapyandimmunoregulationinpancancer
AT chuanleiwang thepotentialroleofcuproptosisrelatedgenesfortherapyandimmunoregulationinpancancer
AT yaozhi thepotentialroleofcuproptosisrelatedgenesfortherapyandimmunoregulationinpancancer
AT jiali thepotentialroleofcuproptosisrelatedgenesfortherapyandimmunoregulationinpancancer
AT jianpengzhou potentialroleofcuproptosisrelatedgenesfortherapyandimmunoregulationinpancancer
AT chuanleiwang potentialroleofcuproptosisrelatedgenesfortherapyandimmunoregulationinpancancer
AT yaozhi potentialroleofcuproptosisrelatedgenesfortherapyandimmunoregulationinpancancer
AT jiali potentialroleofcuproptosisrelatedgenesfortherapyandimmunoregulationinpancancer