An Integrated Systematic Analysis and the Clinical Significance of Hepcidin in Common Malignancies of the Male Genitourinary System

Overview

Journal Front Genet

Date 2022 Jun 1

PMID 35646093

Authors

Xiaogang Wang

Qianqian Shi

Pengfeng Gong

Cuixing Zhou

Yunjie Cao

Affiliations

Soon will be listed here.

Abstract

Tumors of the male genitourinary system are of great concern to the health of men worldwide. Although emerging experiment-based evidence indicates an association between hepcidin and such cancers, an integrated analysis is still lacking. For this reason, in this study, we determined the underlying oncogenic functions of hepcidin in common male genitourinary system tumors, including bladder urothelial carcinoma (BLCA), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), prostate adenocarcinoma (PRAD), and testicular germ cell tumors (TGCT) according to the data from The Cancer Genome Atlas. We found that hepcidin was highly expressed in kidney and testicular cancers. Meanwhile, the expression level of hepcidin was distinctly associated with the prognosis and immune cell infiltration in male patients with certain genitourinary system cancers, especially in KIRC. Elevated hepcidin levels also present as a risk factor in male genitourinary system tumors. Moreover, enrichment analyses revealed that some of the principal associated signaling pathways involving hepcidin and its related genes are identified as tumorigenesis-related. Immunofluorescence staining confirmed the conclusion of our immune infiltration analysis in KIRC tissue. In this study, for the first time, we provided evidence for the oncogenic function of hepcidin in different types of male genitourinary system tumors.

Citing Articles

Transferrin Receptor 2 in Canine Testicular Tumors: An Emerging Key Role in Seminomas.

Leandri R, Buonocore S, Power K Animals (Basel). 2025; 15(2).

PMID: 39858264 PMC: 11758335. DOI: 10.3390/ani15020264.

Hepcidin Is a Valuable Therapeutic Target for Colorectal Cancer.

Frascatani R, Colella M, Monteleone G Cancers (Basel). 2024; 16(23).

PMID: 39682254 PMC: 11640601. DOI: 10.3390/cancers16234068.

HIF2α, Hepcidin and their crosstalk as tumour-promoting signalling.

Formica V, Riondino S, Morelli C, Guerriero S, DAmore F, Di Grazia A Br J Cancer. 2023; 129(2):222-236.

PMID: 37081189 PMC: 10338631. DOI: 10.1038/s41416-023-02266-2.

Ferroptosis landscape in prostate cancer from molecular and metabolic perspective.

Liang J, Liao Y, Wang P, Yang K, Wang Y, Wang K Cell Death Discov. 2023; 9(1):128.

PMID: 37061523 PMC: 10105735. DOI: 10.1038/s41420-023-01430-0.

Hepcidin is upregulated and is a potential therapeutic target associated with immunity in glioma.

Dong T, Zhang B, Zhang R, Wang C, Liu X, Wang F Front Oncol. 2022; 12:963096.

PMID: 36237302 PMC: 9552819. DOI: 10.3389/fonc.2022.963096.

References

Blanchette-Farra N, Kita D, Konstorum A, Tesfay L, Lemler D, Hegde P . Contribution of three-dimensional architecture and tumor-associated fibroblasts to hepcidin regulation in breast cancer. Oncogene. 2018; 37(29):4013-4032. PMC: 6054540. DOI: 10.1038/s41388-018-0243-y. View

Alberta J, Rundell K, Stiles C . Identification of an activity that interacts with the 3'-untranslated region of c-myc mRNA and the role of its target sequence in mediating rapid mRNA degradation. J Biol Chem. 1994; 269(6):4532-8. View

Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P . A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2000; 276(11):7811-9. DOI: 10.1074/jbc.M008923200. View

Lelievre P, Sancey L, Coll J, Deniaud A, Busser B . Iron Dysregulation in Human Cancer: Altered Metabolism, Biomarkers for Diagnosis, Prognosis, Monitoring and Rationale for Therapy. Cancers (Basel). 2020; 12(12). PMC: 7761132. DOI: 10.3390/cancers12123524. View

Linehan W, Ricketts C . The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications. Nat Rev Urol. 2019; 16(9):539-552. DOI: 10.1038/s41585-019-0211-5. View

Chandrashekar D, Bashel B, Balasubramanya S, Creighton C, Ponce-Rodriguez I, Chakravarthi B . UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017; 19(8):649-658. PMC: 5516091. DOI: 10.1016/j.neo.2017.05.002. View

Abd Elmonem E, Tharwa E, Farag M, Fawzy A, El Shinnawy S, Suliman S . Hepcidin mRNA level as a parameter of disease progression in chronic hepatitis C and hepatocellular carcinoma. J Egypt Natl Canc Inst. 2011; 21(4):333-42. View

Yuzhalin A, Urbonas T, Silva M, Muschel R, Gordon-Weeks A . A core matrisome gene signature predicts cancer outcome. Br J Cancer. 2018; 118(3):435-440. PMC: 5808042. DOI: 10.1038/bjc.2017.458. View

Scimeca M, Bonanno E . New highlight in breast cancer development: the key role of hepcidin and iron metabolism. Ann Transl Med. 2019; 6(Suppl 1):S56. PMC: 6291555. DOI: 10.21037/atm.2018.10.30. View

10.

Gao J, Aksoy B, Dogrusoz U, Dresdner G, Gross B, Sumer S . Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6(269):pl1. PMC: 4160307. DOI: 10.1126/scisignal.2004088. View

11.

Zhang C, Zhao N, Zhang X, Xiao J, Li J, Lv D . SurvivalMeth: a web server to investigate the effect of DNA methylation-related functional elements on prognosis. Brief Bioinform. 2020; 22(3). DOI: 10.1093/bib/bbaa162. View

12.

Sanchez-Vega F, Mina M, Armenia J, Chatila W, Luna A, La K . Oncogenic Signaling Pathways in The Cancer Genome Atlas. Cell. 2018; 173(2):321-337.e10. PMC: 6070353. DOI: 10.1016/j.cell.2018.03.035. View

13.

Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q . TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020; 48(W1):W509-W514. PMC: 7319575. DOI: 10.1093/nar/gkaa407. View

14.

Fan Y, Liu B, Chen F, Song Z, Han B, Meng Y . Hepcidin Upregulation in Lung Cancer: A Potential Therapeutic Target Associated With Immune Infiltration. Front Immunol. 2021; 12:612144. PMC: 8047218. DOI: 10.3389/fimmu.2021.612144. View

15.

Wu X, Su D, Wang L, Yu F . Roles of the hepcidin-ferroportin axis and iron in cancer. Eur J Cancer Prev. 2013; 23(2):122-33. DOI: 10.1097/CEJ.0b013e3283627f14. View

16.

Modhukur V, Iljasenko T, Metsalu T, Lokk K, Laisk-Podar T, Vilo J . MethSurv: a web tool to perform multivariable survival analysis using DNA methylation data. Epigenomics. 2017; 10(3):277-288. DOI: 10.2217/epi-2017-0118. View

17.

Jerzak K, Lohmann A, Ennis M, Nemeth E, Ganz T, Goodwin P . Prognostic associations of plasma hepcidin in women with early breast cancer. Breast Cancer Res Treat. 2020; 184(3):927-935. PMC: 7883934. DOI: 10.1007/s10549-020-05903-z. View

18.

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

19.

Sacco A, Battaglia A, Botta C, Aversa I, Mancuso S, Costanzo F . Iron Metabolism in the Tumor Microenvironment-Implications for Anti-Cancer Immune Response. Cells. 2021; 10(2). PMC: 7913036. DOI: 10.3390/cells10020303. View

20.

Bardou P, Mariette J, Escudie F, Djemiel C, Klopp C . jvenn: an interactive Venn diagram viewer. BMC Bioinformatics. 2014; 15:293. PMC: 4261873. DOI: 10.1186/1471-2105-15-293. View