Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma

Abstract Background Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). Methods Multiple Gene Express...

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Main Authors: Jiaming Su, Guanlin Zhong, Weiling Qin, Lu Zhou, Jiemei Ye, Yinxing Ye, Chang Chen, Pan Liang, Weilin Zhao, Xue Xiao, Wensheng Wen, Wenqi Luo, Xiaoying Zhou, Zhe Zhang, Yonglin Cai, Cheng Li
Format: Article
Language:English
Published: Springer 2024-04-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-024-00969-3
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author Jiaming Su
Guanlin Zhong
Weiling Qin
Lu Zhou
Jiemei Ye
Yinxing Ye
Chang Chen
Pan Liang
Weilin Zhao
Xue Xiao
Wensheng Wen
Wenqi Luo
Xiaoying Zhou
Zhe Zhang
Yonglin Cai
Cheng Li
author_facet Jiaming Su
Guanlin Zhong
Weiling Qin
Lu Zhou
Jiemei Ye
Yinxing Ye
Chang Chen
Pan Liang
Weilin Zhao
Xue Xiao
Wensheng Wen
Wenqi Luo
Xiaoying Zhou
Zhe Zhang
Yonglin Cai
Cheng Li
author_sort Jiaming Su
collection DOAJ
description Abstract Background Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). Methods Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. Results A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan–Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model’s accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8+ T cells, CD4+ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry. Conclusion This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.
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spelling doaj.art-3e09ea546322402c9f2b0152f2bc93252024-04-14T11:20:03ZengSpringerDiscover Oncology2730-60112024-04-0115111710.1007/s12672-024-00969-3Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinomaJiaming Su0Guanlin Zhong1Weiling Qin2Lu Zhou3Jiemei Ye4Yinxing Ye5Chang Chen6Pan Liang7Weilin Zhao8Xue Xiao9Wensheng Wen10Wenqi Luo11Xiaoying Zhou12Zhe Zhang13Yonglin Cai14Cheng Li15Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Clinical Laboratory, Wuzhou Red Cross HospitalDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityGuangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross HospitalDepartment of Clinical Laboratory, Wuzhou Red Cross HospitalDepartment of Pathology, Wuzhou Red Cross HospitalDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pathology, Affiliated Tumor Hospital of Guangxi Medical UniversityKey Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of EducationDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Clinical Laboratory, Wuzhou Red Cross HospitalDepartment of Pathology, Wuzhou Red Cross HospitalAbstract Background Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). Methods Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. Results A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan–Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model’s accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8+ T cells, CD4+ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry. Conclusion This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.https://doi.org/10.1007/s12672-024-00969-3Nasopharyngeal carcinomaIron metabolismPrognostic signatureTumor microenvironmentFerroptosis
spellingShingle Jiaming Su
Guanlin Zhong
Weiling Qin
Lu Zhou
Jiemei Ye
Yinxing Ye
Chang Chen
Pan Liang
Weilin Zhao
Xue Xiao
Wensheng Wen
Wenqi Luo
Xiaoying Zhou
Zhe Zhang
Yonglin Cai
Cheng Li
Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma
Discover Oncology
Nasopharyngeal carcinoma
Iron metabolism
Prognostic signature
Tumor microenvironment
Ferroptosis
title Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma
title_full Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma
title_fullStr Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma
title_full_unstemmed Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma
title_short Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma
title_sort integrating iron metabolism related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma
topic Nasopharyngeal carcinoma
Iron metabolism
Prognostic signature
Tumor microenvironment
Ferroptosis
url https://doi.org/10.1007/s12672-024-00969-3
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