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The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma

Background: Reliable biomarkers are rare for renal cell carcinoma (RCC) treatment selection. We aimed to discover novel biomarkers for precision medicine. The iron-regulating hormone hepcidin (HAMP) was reportedly increased in RCC patient sera and tissues. However, its potential implication as a pro...

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Autores principales: Huang, Jian, Liu, Wang, Song, Shiqi, Li, Jean C., Gan, Kaimei, Shen, Chunxiao, Holzbeierlein, Jeffrey, Li, Benyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757070/
https://www.ncbi.nlm.nih.gov/pubmed/36532749
http://dx.doi.org/10.3389/fphar.2022.1080055
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author Huang, Jian
Liu, Wang
Song, Shiqi
Li, Jean C.
Gan, Kaimei
Shen, Chunxiao
Holzbeierlein, Jeffrey
Li, Benyi
author_facet Huang, Jian
Liu, Wang
Song, Shiqi
Li, Jean C.
Gan, Kaimei
Shen, Chunxiao
Holzbeierlein, Jeffrey
Li, Benyi
author_sort Huang, Jian
collection PubMed
description Background: Reliable biomarkers are rare for renal cell carcinoma (RCC) treatment selection. We aimed to discover novel biomarkers for precision medicine. The iron-regulating hormone hepcidin (HAMP) was reportedly increased in RCC patient sera and tissues. However, its potential implication as a prognostic biomarker remains exclusive. Methods: Multiple RNA-seq and cDNA microarray datasets were utilized to analyze gene expression profiles. Hepcidin protein expression was assessed using an ELISA assay in cell culture models. Comparisons of gene expression profiles and patient survival outcomes were conducted using the R package bioinformatics software. Results: Five (HAMP, HBS, ISCA2, STEAP2, and STEAP3) out of 71 iron-modulating genes exhibited consistent changes along with tumor stage, lymph node invasion, distal metastasis, tumor cell grade, progression-free interval, overall survival, and disease-specific survival. Of which HAMP upregulation exerted as a superior factor (AUC = 0.911) over the other four genes in distinguishing ccRCC tissue from normal renal tissue. HAMP upregulation was tightly associated with its promoter hypomethylation and immune checkpoint factors (PDCD1, LAG3, TIGIT, and CTLA4). Interleukin-34 (IL34) treatment strongly enhanced hepcidin expression in renal cancer Caki-1 cells. Patients with higher levels of HAMP expression experienced worse survival outcomes. Conclusion: These data suggest that HAMP upregulation is a potent prognostic factor of poor survival outcomes and a novel immunotherapeutic biomarker for ccRCC patients.
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spelling pubmed-97570702022-12-17 The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma Huang, Jian Liu, Wang Song, Shiqi Li, Jean C. Gan, Kaimei Shen, Chunxiao Holzbeierlein, Jeffrey Li, Benyi Front Pharmacol Pharmacology Background: Reliable biomarkers are rare for renal cell carcinoma (RCC) treatment selection. We aimed to discover novel biomarkers for precision medicine. The iron-regulating hormone hepcidin (HAMP) was reportedly increased in RCC patient sera and tissues. However, its potential implication as a prognostic biomarker remains exclusive. Methods: Multiple RNA-seq and cDNA microarray datasets were utilized to analyze gene expression profiles. Hepcidin protein expression was assessed using an ELISA assay in cell culture models. Comparisons of gene expression profiles and patient survival outcomes were conducted using the R package bioinformatics software. Results: Five (HAMP, HBS, ISCA2, STEAP2, and STEAP3) out of 71 iron-modulating genes exhibited consistent changes along with tumor stage, lymph node invasion, distal metastasis, tumor cell grade, progression-free interval, overall survival, and disease-specific survival. Of which HAMP upregulation exerted as a superior factor (AUC = 0.911) over the other four genes in distinguishing ccRCC tissue from normal renal tissue. HAMP upregulation was tightly associated with its promoter hypomethylation and immune checkpoint factors (PDCD1, LAG3, TIGIT, and CTLA4). Interleukin-34 (IL34) treatment strongly enhanced hepcidin expression in renal cancer Caki-1 cells. Patients with higher levels of HAMP expression experienced worse survival outcomes. Conclusion: These data suggest that HAMP upregulation is a potent prognostic factor of poor survival outcomes and a novel immunotherapeutic biomarker for ccRCC patients. Frontiers Media S.A. 2022-12-02 /pmc/articles/PMC9757070/ /pubmed/36532749 http://dx.doi.org/10.3389/fphar.2022.1080055 Text en Copyright © 2022 Huang, Liu, Song, Li, Gan, Shen, Holzbeierlein and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Huang, Jian
Liu, Wang
Song, Shiqi
Li, Jean C.
Gan, Kaimei
Shen, Chunxiao
Holzbeierlein, Jeffrey
Li, Benyi
The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma
title The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma
title_full The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma
title_fullStr The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma
title_full_unstemmed The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma
title_short The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma
title_sort iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757070/
https://www.ncbi.nlm.nih.gov/pubmed/36532749
http://dx.doi.org/10.3389/fphar.2022.1080055
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