NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses

Abstract Despite extensive research highlighting the pivotal role of NOX4 in the development of various malignancies, no systematic pan-cancer analysis has been conducted to evaluate its comprehensive prognostic value and potential immunological functions. In this study, we explored the prognostic s...

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Main Authors: Yusheng Liu, Chunying Wu, Qiang Wang, Xiaoshan Zhao, Xuefeng Jiang
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-03499-2
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author Yusheng Liu
Chunying Wu
Qiang Wang
Xiaoshan Zhao
Xuefeng Jiang
author_facet Yusheng Liu
Chunying Wu
Qiang Wang
Xiaoshan Zhao
Xuefeng Jiang
author_sort Yusheng Liu
collection DOAJ
description Abstract Despite extensive research highlighting the pivotal role of NOX4 in the development of various malignancies, no systematic pan-cancer analysis has been conducted to evaluate its comprehensive prognostic value and potential immunological functions. In this study, we explored the prognostic significance of NOX4 and its role in immune modulation across different cancer types. We performed a pan-cancer analysis of NOX4 expression and its prognostic implications using multiple databases, including TCGA, GEPIA, GTEx, UALCAN, TISCH, GDSC, PDB, TIMER, and cBioPortal. This analysis provided a detailed assessment of NOX4 expression profiles, clinical correlations, genetic variants, tumor microenvironment interactions, immune relevance, therapeutic potential, and related gene functions through various multi-omics approaches. To further investigate these findings, we collected clinical samples from selected cancer types and validated NOX4 expression through immunohistochemistry, H&E staining, and RT-PCR. Our results revealed that NOX4 was overexpressed in most tumors, although its expression was significantly reduced in certain renal cancers. Moreover, we observed distinct correlations between NOX4 expression and patient prognosis. Notably, NOX4 expression was significantly associated with tumor infiltration, indicating its potential as a target for immunotherapy. Additionally, NOX4 expression showed significant correlations with immune checkpoint proteins (ICP), tumor mutation burden (TMB), microsatellite instability (MSI), RNA stemness scores (RNAss), DNA stemness scores (DNAss), RNA methylation, and DNA methylation.
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spelling doaj-art-58fbc52dd76c4ddcbda7a77e49651b5d2025-08-20T02:03:31ZengNature PortfolioScientific Reports2045-23222025-05-0115112210.1038/s41598-025-03499-2NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analysesYusheng Liu0Chunying Wu1Qiang Wang2Xiaoshan Zhao3Xuefeng Jiang4Department of Traditional Chinese Medicine, Yangjiang People’s HospitalDepartment of Traditional Chinese Medicine, Yangjiang People’s HospitalDepartment of Traditional Chinese Medicine, Yangjiang People’s HospitalDepartment of Traditional Chinese Medicine, Yangjiang People’s HospitalDepartment of Traditional Chinese Medicine, Yangjiang People’s HospitalAbstract Despite extensive research highlighting the pivotal role of NOX4 in the development of various malignancies, no systematic pan-cancer analysis has been conducted to evaluate its comprehensive prognostic value and potential immunological functions. In this study, we explored the prognostic significance of NOX4 and its role in immune modulation across different cancer types. We performed a pan-cancer analysis of NOX4 expression and its prognostic implications using multiple databases, including TCGA, GEPIA, GTEx, UALCAN, TISCH, GDSC, PDB, TIMER, and cBioPortal. This analysis provided a detailed assessment of NOX4 expression profiles, clinical correlations, genetic variants, tumor microenvironment interactions, immune relevance, therapeutic potential, and related gene functions through various multi-omics approaches. To further investigate these findings, we collected clinical samples from selected cancer types and validated NOX4 expression through immunohistochemistry, H&E staining, and RT-PCR. Our results revealed that NOX4 was overexpressed in most tumors, although its expression was significantly reduced in certain renal cancers. Moreover, we observed distinct correlations between NOX4 expression and patient prognosis. Notably, NOX4 expression was significantly associated with tumor infiltration, indicating its potential as a target for immunotherapy. Additionally, NOX4 expression showed significant correlations with immune checkpoint proteins (ICP), tumor mutation burden (TMB), microsatellite instability (MSI), RNA stemness scores (RNAss), DNA stemness scores (DNAss), RNA methylation, and DNA methylation.https://doi.org/10.1038/s41598-025-03499-2NOX4Pan-cancerPrognosisImmune microenvironment
spellingShingle Yusheng Liu
Chunying Wu
Qiang Wang
Xiaoshan Zhao
Xuefeng Jiang
NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses
Scientific Reports
NOX4
Pan-cancer
Prognosis
Immune microenvironment
title NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses
title_full NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses
title_fullStr NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses
title_full_unstemmed NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses
title_short NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses
title_sort nox4 as an emerging prognostic and immunological biomarker across pan cancer analyses
topic NOX4
Pan-cancer
Prognosis
Immune microenvironment
url https://doi.org/10.1038/s41598-025-03499-2
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AT chunyingwu nox4asanemergingprognosticandimmunologicalbiomarkeracrosspancanceranalyses
AT qiangwang nox4asanemergingprognosticandimmunologicalbiomarkeracrosspancanceranalyses
AT xiaoshanzhao nox4asanemergingprognosticandimmunologicalbiomarkeracrosspancanceranalyses
AT xuefengjiang nox4asanemergingprognosticandimmunologicalbiomarkeracrosspancanceranalyses