Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment
Background Despite the association of ferroptosis with various tumors, the specific mechanism by which it influences colon adenocarcinoma (COAD) microenvironmental equilibrium remains elusive. This study aims to elucidate how ferroptosis affects COAD microenvironmental homeostasis and its potential...
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PeerJ Inc.
2023-06-01
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| Online Access: | https://peerj.com/articles/15476.pdf |
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| author | Yuanyuan Xu Qingzhu Tang Ning Ding Tao Zhang Hongbiao Luo |
| author_facet | Yuanyuan Xu Qingzhu Tang Ning Ding Tao Zhang Hongbiao Luo |
| author_sort | Yuanyuan Xu |
| collection | DOAJ |
| description | Background Despite the association of ferroptosis with various tumors, the specific mechanism by which it influences colon adenocarcinoma (COAD) microenvironmental equilibrium remains elusive. This study aims to elucidate how ferroptosis affects COAD microenvironmental homeostasis and its potential impact on COAD research. Objective By employing genetic screening and single-cell analysis of tumor data, we investigated the role of ferroptosis genes in COAD microenvironmental homeostasis. The genes were correlated with immune cell infiltration in tissue samples and patient outcomes. Methods Ferroptosis-associated genes were initially identified through the FerrDb database. Utilizing the tidyverse and Seurat packages, genes with substantial expression differences were extracted, and clustering analysis was performed on the single-cell data. A Venn diagram depicted shared differential genes for ferroptosis and tumors. To screen key ferroptosis genes, further enrichment analysis and immune cell infiltration analysis were conducted. Lastly, human COAD cell lines were employed to overexpress CDGSH iron sulfur domain 2 (CISD2) through cellular assays to validate its function in COAD. Results Following screening of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, 414 COAD patient samples and 341 normal samples were included. Through the FerrDb database, 259 ferroptosis genes were identified. Clustering the single-cell data revealed 911 tumor marker genes, of which 18 were ferroptosis genes. Analysis of variance (ANOVA) and univariate regression analysis determined that only CISD2 was statistically significantly associated with clinical outcomes. Additionally, CISD2 was found to positively correlate with activated memory T cells and negatively correlate with regulatory T cells (Tregs) and plasma cells in COAD, as well as being significantly associated with several immune-related and cancer-related pathways. CISD2 expression was elevated in most tumors, likely due to cell cycle regulation and immune system activation. Moreover, CISD2 upregulation inhibited COAD cell proliferation and enhanced 5-fluorouracil (5-FU) sensitivity. Our findings indicate, for the first time, that CISD2 governs the cell cycle and stimulates the immune system to impede COAD progression. Conclusion By modulating the cell cycle and mediating immune infiltration, CISD2 may inhibit COAD development by influencing tumor immune microenvironment equilibrium, providing valuable insights into the relevance and potential impact of the research results on the COAD research field. |
| first_indexed | 2024-03-09T07:02:11Z |
| format | Article |
| id | doaj.art-5dc69f8ab25f459da23b582578007faf |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:02:11Z |
| publishDate | 2023-06-01 |
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| spelling | doaj.art-5dc69f8ab25f459da23b582578007faf2023-12-03T09:51:04ZengPeerJ Inc.PeerJ2167-83592023-06-0111e1547610.7717/peerj.15476Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironmentYuanyuan Xu0Qingzhu Tang1Ning Ding2Tao Zhang3Hongbiao Luo4Department of Anorectal Surgery, Chenzhou No. 1 People’s Hospital, Chenzhou, ChinaDepartment of Anorectal Surgery, Chenzhou No. 1 People’s Hospital, Chenzhou, ChinaHunan University of Chinese Medicine, Hunan, ChinaHunan University of Chinese Medicine, Hunan, ChinaDepartment of Anorectal Surgery, Chenzhou No. 1 People’s Hospital, Chenzhou, ChinaBackground Despite the association of ferroptosis with various tumors, the specific mechanism by which it influences colon adenocarcinoma (COAD) microenvironmental equilibrium remains elusive. This study aims to elucidate how ferroptosis affects COAD microenvironmental homeostasis and its potential impact on COAD research. Objective By employing genetic screening and single-cell analysis of tumor data, we investigated the role of ferroptosis genes in COAD microenvironmental homeostasis. The genes were correlated with immune cell infiltration in tissue samples and patient outcomes. Methods Ferroptosis-associated genes were initially identified through the FerrDb database. Utilizing the tidyverse and Seurat packages, genes with substantial expression differences were extracted, and clustering analysis was performed on the single-cell data. A Venn diagram depicted shared differential genes for ferroptosis and tumors. To screen key ferroptosis genes, further enrichment analysis and immune cell infiltration analysis were conducted. Lastly, human COAD cell lines were employed to overexpress CDGSH iron sulfur domain 2 (CISD2) through cellular assays to validate its function in COAD. Results Following screening of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, 414 COAD patient samples and 341 normal samples were included. Through the FerrDb database, 259 ferroptosis genes were identified. Clustering the single-cell data revealed 911 tumor marker genes, of which 18 were ferroptosis genes. Analysis of variance (ANOVA) and univariate regression analysis determined that only CISD2 was statistically significantly associated with clinical outcomes. Additionally, CISD2 was found to positively correlate with activated memory T cells and negatively correlate with regulatory T cells (Tregs) and plasma cells in COAD, as well as being significantly associated with several immune-related and cancer-related pathways. CISD2 expression was elevated in most tumors, likely due to cell cycle regulation and immune system activation. Moreover, CISD2 upregulation inhibited COAD cell proliferation and enhanced 5-fluorouracil (5-FU) sensitivity. Our findings indicate, for the first time, that CISD2 governs the cell cycle and stimulates the immune system to impede COAD progression. Conclusion By modulating the cell cycle and mediating immune infiltration, CISD2 may inhibit COAD development by influencing tumor immune microenvironment equilibrium, providing valuable insights into the relevance and potential impact of the research results on the COAD research field.https://peerj.com/articles/15476.pdfscRNA-seqFerroptosisCISD2Colon Adenocarcinoma (COAD)Tumor microenvironment homeostasis |
| spellingShingle | Yuanyuan Xu Qingzhu Tang Ning Ding Tao Zhang Hongbiao Luo Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment PeerJ scRNA-seq Ferroptosis CISD2 Colon Adenocarcinoma (COAD) Tumor microenvironment homeostasis |
| title | Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment |
| title_full | Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment |
| title_fullStr | Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment |
| title_full_unstemmed | Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment |
| title_short | Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment |
| title_sort | ferroptosis associated gene cisd2 suppresses colon cancer development by regulating tumor immune microenvironment |
| topic | scRNA-seq Ferroptosis CISD2 Colon Adenocarcinoma (COAD) Tumor microenvironment homeostasis |
| url | https://peerj.com/articles/15476.pdf |
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