Abstract
Background
Epiregulin is a molecule that plays a role in cell proliferation, tumor development, inflammation, and angiogenesis in malignant diseases.
Aim
Our study aims to reveal, for the first time, the predictive value of this molecule in non-Hodgkin lymphoma (NHL) and its association with disease stage, cell type, and extranodal involvement.
Methods
The study is an observational case–control trial involving 60 newly diagnosed NHL patients and 60 healthy individuals (control group) between 18 and 75 years old. Demographic characteristics of all volunteers, stages of patients’ illnesses and lymphoma cell types, hemogram, biochemistry tests, beta 2-microglobulin, C-reactive protein (CRP), and epiregulin levels were measured and statistically evaluated.
Results
Epiregulin levels were significantly higher in NHL patients compared to the control group (P < 0.0001). Similarly, a significant increase in epiregulin levels was observed in advanced NHL patients. Furthermore, the most common NHL subgroup within the NHL group, diffuse Large B Cell Lymphoma (DLBCL), and the subgroup with extranodal involvement also had significantly higher levels of epiregulin. A positive correlation was found between the epiregulin molecule and CRP, beta 2-microglobulin, and lactate dehydrogenase (LDH) levels in NHL patients.
Conclusion
Our study suggests that serum epiregulin levels, discovered to increase in NHL patients for the first time, may be an independent predictive molecule in an advanced stage, extranodal involvement, and the DLBCL subtype of this disease. Epiregulin positively correlates with prognostic molecules such as beta 2-microglobulin, LDH, and CRP. Illuminating its potential role in NHL pathogenesis could make epiregulin a vital drug target for treatment.
Similar content being viewed by others
Data availability
Data and materials are reachable from hospital automation information systems.
References
Cai W, Zeng Q, Zhang X et al (2021) Trends analysis of non-Hodgkin lymphoma at the national, regional, and global level, 1990–2019: results from the global burden of disease study 2019. Front Med 8:738693. https://doi.org/10.3389/fmed.2021.738693
Armitage JO, Gascoyne RD, Lunning MA et al (2017) Non-Hodgkin lymphoma. Lancet (London, England) 390(10091):298–310. https://doi.org/10.1016/S0140-6736(16)32407-2
Thandra KC, Barsouk A, Saginala K et al (2021) Epidemiology of non-Hodgkin’s lymphoma. Med Sci (Basel, Switzerland) 9(1):5. https://doi.org/10.3390/medsci9010005
Müller AM, Ihorst G, Mertelsmann R et al (2005) Epidemiology of non-Hodgkin’s lymphoma (NHL): trends, geographic distribution, and etiology. Ann Hematol 84(1):1–12. https://doi.org/10.1007/s00277-004-0939-7
Aldinucci D, Gloghini A, Pinto A et al (2010) The classical Hodgkin’s lymphoma microenvironment and its role in promoting tumour growth and immune escape. J Pathol 221(3):248–263. https://doi.org/10.1002/path.2711
Toyoda H, Komurasaki T, Uchida D et al (1997) Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. Biochem J 326:69–75. https://doi.org/10.1042/bj3260069
Lindvall C, Hou M, Komurasaki T et al (2003) Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene. Cancer Res 63(8):1743–1747
Liebmann C (2011) EGF receptor activation by GPCRs: an universal pathway reveals different versions. Mol Cell Endocrinol 331(2):222–231. https://doi.org/10.1016/j.mce.2010.04.008
Riese DJ 2nd, Cullum RL (2014) Epiregulin: roles in normal physiology and cancer. Semin Cell Dev Biol 28:49–56. https://doi.org/10.1016/j.semcdb.2014.03.005
Bauer AK, Velmurugan K, Xiong KN et al (2017) Epiregulin is required for lung tumor promotion in a murine two-stage carcinogenesis model. Mol Carcinog 56(1):94–105. https://doi.org/10.1002/mc.22475
Charlson ME, Carrozzino D, Guidi J et al (2022) Charlson comorbidity index: a critical review of clinimetric properties. Psychother Psychosom 91(1):8–35. https://doi.org/10.1159/000521288
Schneider MR, Wolf E (2009) The epidermal growth factor receptor ligands at a glance. J Cell Physiol 218(3):460–466. https://doi.org/10.1002/jcp.21635
McIntyre E, Blackburn E, Brown PJ et al (2010) The complete family of epidermal growth factor receptors and their ligands are co-ordinately expressed in breast cancer. Breast Cancer Res Treat 122(1):105–110. https://doi.org/10.1007/s10549-009-0536-5
Hayashida T, Takahashi F, Chiba N et al (2010) HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci USA 107(3):1100–1105. https://doi.org/10.1073/pnas.0912710107
Kometani T, Yoshino I, Miura N et al (2009) Benzo[a]pyrene promotes proliferation of human lung cancer cells by accelerating the epidermal growth factor receptor signaling pathway. Cancer Lett 278(1):27–33. https://doi.org/10.1016/j.canlet.2008.12.017
Zhang J, Iwanaga K, Choi KC et al (2008) Intratumoral epiregulin is a marker of advanced disease in non-small cell lung cancer patients and confers invasive properties on EGFR-mutant cells. Cancer Prev Res (Philadelphia, Pa.) 1(3):201–207. https://doi.org/10.1158/1940-6207.CAPR-08-0014
Bormann F, Stinzing S, Tierling S et al (2019) Epigenetic regulation of amphiregulin and epiregulin in colorectal cancer. Int J Cancer 144(3):569–581. https://doi.org/10.1002/ijc.31892
Wang C, Long Q, Fu Q et al (2022) Targeting epiregulin in the treatment-damaged tumor microenvironment restrains therapeutic resistance. Oncogene 41(45):4941–4959. https://doi.org/10.1038/s41388-022-02476-7
Kamimura D, Arima Y, Kohsaka H et al (2015) Temporal expression of growth factors triggered by epiregulin regulates inflammation development. J Immunol 194(3):1039–1046. https://doi.org/10.4049/jimmunol.1400562
Child JA, Spati B, Illingworth S et al (1980) Serum beta 2 microglobulin and C-reactive protein in the monitoring of lymphomas findings in a multicenter study and experience in selected patients. Cancer 45(2):318–326. https://doi.org/10.1002/1097-0142(19800115)45:2%3c318::aid-cncr2820450220%3e3.0.co;2-c
Wu L, Wang T, Gui W et al (2014) Prognostic significance of serum beta-2 microglobulin in patients with non-Hodgkin lymphoma. Oncology 87(1):40–47. https://doi.org/10.1159/000362670
Taylor DS, Cheng X, Pawlowski JE et al (1999) Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. Proc Natl Acad Sci USA 96(4):1633–1638. https://doi.org/10.1073/pnas.96.4.1633
Author information
Authors and Affiliations
Contributions
Conceptualization: ID, OYA, OB; data curation: ID, OYA, GB; formal analysis: ID, IY, GB; investigation: ID, IY, FB; methodology: ID, FB, OB; supervision: OB, IY, GB; visualization: ID, IY, OYA; writing—original draft: ID, FB, IY; writing—review and editing: ID, IY, FB, OYA. All authors have read and approved the final version.
Corresponding author
Ethics declarations
Ethical approval
This study was reviewed and approved by the institutional review board for exemption.
Consent to participate
Informed consent was obtained from all participants included in the study.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Demir, I., Akan, O.Y., Bilgir, F. et al. Epiregulin: A new prognostic molecule in non-Hodgkin lymphoma. Ir J Med Sci (2024). https://doi.org/10.1007/s11845-024-03609-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11845-024-03609-5