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Some studies suggest the potential involvement of ISCA1 in tumor progression through interactions with ferroptosis-related genes (FRGs) and the tumor immune microenvironment (TME). However, there has been no systematic analysis of its role in FRGs and the TME or its predictive value for prognosis and immunotherapy response across different cancer types. Methods: In this study, we analyzed the expression and prognosis of ISCA1 RNA, CNV, methylation, and protein in multiple tumor tissues via data from the TCGA and CPTAC databases and clinical information. We conducted a comprehensive analysis of the correlations between ISCA1 and FRGs, immune-related genes (including immune regulatory genes and immune checkpoint genes), immune cell infiltration, immune infiltration scores, tumor stemness, and genomic heterogeneity. Results: We performed drug prediction and validation through molecular docking and molecular dynamics analysis to identify candidate drugs that could promote or inhibit ISCA1 RNA expression. Our findings revealed that ISCA1 could serve as a biomarker in thyroid carcinoma, play a role with different FRGs in various cell types, and mediate different ligand\u2013receptor pathways for cell\u2013cell communication. Conclusions: Overall, our study highlights the potential of ISCA1 as a novel biomarker for predicting prognosis and immunotherapeutic efficacy in thyroid carcinoma and suggests its potential for developing novel antitumor drugs or improving immunotherapy.<\/jats:p>","DOI":"10.3390\/genes15121538","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T10:19:42Z","timestamp":1732789182000},"page":"1538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comprehensive Analysis Reveals That ISCA1 Is Correlated with Ferroptosis-Related Genes Across Cancers and Is a Biomarker in Thyroid Carcinoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Dejun","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Nantong University, Nantong 226019, China"},{"name":"Department of Respiratory Medicine, Affiliated Nantong Hospital of Shanghai University, Nantong 226011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6120-7318","authenticated-orcid":false,"given":"Xiaorong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Jiangyin People\u2019s Hospital Affiliated to Nantong University, Jiangyin 214499, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","first-page":"221","article-title":"[Cancer incidence and mortality in China, 2022]","volume":"46","author":"Zheng","year":"2024","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/j.bbagen.2017.05.019","article-title":"Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy","volume":"1861","year":"2017","journal-title":"Biochim. 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