Possible relevance of epidermal growth factor as a biomarker of inflammation in severe COVID-19
Keywords:
serum biomarkers/inflammation, Epidermal growth factor, COVID-19Abstract
Background: EGFR plays a critical role in inflammation at the pulmonary level. Data exploring the role of its canonical ligand are scarce. Exploration of new and potential biomarkers expands diagnostic and therapeutic options, providing resilience in complex healthcare settings.
Aim: To explore the variability of serum EGF levels according to sex, age and clinical status in subjects with COVID-19 vs. control, as well as to determine possible notable correlates.
Methods: Controlled cross-sectional exploratory study with quota sampling in patients with COVID-19 admitted to the Saturnino Lora Hospital. The commercial kit UMELISA EGF from the Cuban Immunoassay Center was used for EGF determinations.
Results: Significant differences were observed with respect to serum EGF values in COVID-19 vs. controls (g = 0.6603, p = 0.0021). Serum EGF values < 200 pg /mL were associated with the risk of worse clinical status (OR = 30.8, HR = 11.19 CI95%: 1.82-10.79, X2 = 17.42, p = 0.000*). No biologically relevant differences were observed between sexes (p=0.7694); Regarding age, slight differences in the effect were observed (g = 0.4232, p = 0.0527). A higher probability of obtaining serum EGF values > 200 pg /mL was identified in patients ≤ 65 years (HR = 2.5 CI95 %: 1.06-3.03, p = 0.0308). Serum EGF in relation to NLR (β = 0.2232, p = 0.0353) and PLR (β = 0.2117, p = 0.0411) behaved as a predictor of inflammation in that condition.
Conclusions: Serum EGF determination may be a presumed independent marker of inflammation with implications for the pathophysiology of SARS-CoV-2 pneumopathy.
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1. Morty RE, Ziebuhr J. The pathophysiology of COVID-19 and SARS-CoV-2 infection. Am J Physiol Lung Cell Mol Physiol. 2020 [accessed 01/12/2023];318(5):L1016-9. Available at: https://pubmed.ncbi.nlm.nih.gov/32266822/
2. Rabaan AA, Al-Ahmed SH, Haque S, Sah R, Tiwari R, Malik YS, et al. SARS-CoV-2, SARS-CoV and MERS-COV: a comparative overview. Infez Med. 2020 [accessed 01/12/2023];28(2). Available at: https://pubmed.ncbi.nlm.nih.gov/32275259/
3. Kakodkar P, Kaka N, Baig MN. A comprehensive review of the literature on the clinical presentation and management of the 2019 coronavirus disease pandemic (COVID-19). Cureus. 2020 [accessed 01/12/2023];12(4). Available at: https://pubmed.ncbi.nlm.nih.gov/32269893/
4. Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020 [accessed 01/12/2023];92(4):418-23. Available at: https://pubmed.ncbi.nlm.nih.gov/31967327/
5. Qian YR, Guo YI, Wan HY, Fan L, Feng Y, Ni L, et al. Angiotensin-converting enzyme 2 attenuates non-small cell lung cancer metastasis through inhibition of epithelial-mesenchymal transition. Oncol Rep. 2013 [accessed 01/12/2023];29(6):2408-14. Available at: https://pubmed.ncbi.nlm.nih.gov/23545945/
6. Zhong J, Li L, Wang Z, Bai H, Gai F, Duan J, et al. Potential resistance mechanisms revealed by targeted sequencing of lung adenocarcinoma patients with primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). J. Thorac Oncol. 2017 [accessed 01/12/2023];12(12):1766-78. Available at: https://pubmed.ncbi.nlm.nih.gov/28818608/
7. Deben C, Le Compte M, Siozopoulou V, Lambrechts H, Hermans C, Lau HW, et al. Expression of SARS-CoV-2-related surface proteins in patients with non-small cell lung cancer and the influence of standard-of-care therapy. Cancers (Basel). 2022 [accessed 01/12/2023];14(17):4074. Available at: https://pubmed.ncbi.nlm.nih.gov/36077610/
8. Engler M, Albers D, Von Maltitz P, Groß R, Münch J, Cirstea IC. ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection. Life Sciences Alliance. 2023 [accessed 01/12/2023];6(9):e202201880. Available at: https://pubmed.ncbi.nlm.nih.gov/37402592/
9. Yoo J, Perez CER, Nie W, Edwards RA, Sinnett-Smith J, Rozengurt E. TNF-α induces positive regulation of EGFR expression and signaling in human colon myofibroblasts. Am J Physiol Gastrointest Liver Physiol. 2012 [accessed 01/12/2023];302(8):G805-14. Available at: https://pubmed.ncbi.nlm.nih.gov/22301110/
10. Yoo J, Rodriguez Perez CE, Nie W, Sinnett-Smith J, Rozengurt E. TNF-α and LPA promote synergistic COX-2 expression in human colon myofibroblasts: role of LPA-mediated transactivation of positively regulated EGFR. BMC Gastroenterol. 2013 [accessed 01/12/2023];13(1). Available at: https://pubmed.ncbi.nlm.nih.gov/23688423/
11. Chen J, Chen JK, Nagai K, Plieth D, Tan M, Lee TC, et al. EGFR signaling promotes TGFβ-dependent renal fibrosis. J Am Soc Nephrol [Internet]. 2012 [accessed 01/12/2023];23(2):215-24. Available from: https://pubmed.ncbi.nlm.nih.gov/22095949/
12. Zhuang S, Liu N. EGFR signaling in renal fibrosis. Kidney Int Suppl (2011). 2014 [accessed 01/12/2023];4(1):70-4. Available from: https://pubmed.ncbi.nlm.nih.gov/26312153/
13. Luwor RB, Baradaran B, Taylor LE, Iaria J, Nheu TV, Amiry N, et al. Targeting Stat3 and Smad7 to restore TGF- β cytostatic regulation of tumor cells in vitro and in vivo. Oncogene. 2013 [accessed 01/12/2023];32(19):2433-41. Available at: https://pubmed.ncbi.nlm.nih.gov/22751114/
14. Gomes SMR, Brito AC de S, Manfro WFP, Ribeiro-Alves M, Ribeiro RS de A, da Cal MS, et al. High levels of SARS-CoV-2-specific proinflammatory biomarkers revealed by an in vitro whole blood cytokine release assay (CRA) in recovered and long-term COVID-19 patients. PLoS One. 2023 [accessed 01/12/2023];18(4):e0283983. DOI: http://dx.doi.org/10.1371/journal.pone.0283983
15. Ahern DJ, Ai Z, Ainsworth M, Allan C, Allcock A, Angus B, et al. A blood atlas of COVID-19 defines distinguishing features of disease severity and specificity. Cellular [Internet]. 2022 [accessed 01/12/2023];185(5):916-938.e58. Available at: https://pubmed.ncbi.nlm.nih.gov/35216673/
16. Matsuyama T, Kubli SP, Yoshinaga SK, Pfeffer K, Mak TW. An aberrant STAT pathway is central to COVID-19. Cell death differs. 2020 [accessed 01/12/2023];27(12):3209-25. DOI: http://dx.doi.org/10.1038/s41418-020-00633-7
17. Purcaru OS, Artene SA, Barcan E, Silosi CA, Stanciu I, Danoiu S, et al. Crosstalk between SARS-CoV-2 and receptor tyrosine kinase signaling in cancer. Int J Mol Sci. 2021;22(9):4830. DOI: http://dx.doi.org/10.3390/ijms22094830
18. de Almeida SMV, Santos Soares JC, dos Santos KL, Alves JEF, Ribeiro AG, Jacob ITT, et al. COVID-19 therapy: what weapons do we bring to the battle? Bioorg Med Chem. 2020;28(23):115757. DOI: http://dx.doi.org/10.1016/j.bmc.2020.115757
19. Shen Q, Li J, Zhang Z, Guo S, Wang Q, An X, et al. COVID-19: systemic pathology and its implications for therapy. Int J Biol Sci. 2022;18(1):386-408. DOI: http://dx.doi.org/10.7150/ijbs.65911
20. London HD, Armada JJ, Martínez AH, Abdo Cuza AA, Sánchez YH, Rodríguez AG, et al. EGFR blockade with nimotuzumab: a novel strategy for the treatment of COVID-19. Immunotherapy. 2022;14(7):521-30. DOI: http://dx.doi.org/10.2217/imt-2022-0027
21. Saavedra D, Añé -Kourí AL, Gregorich EML, Mena J, Lorenzo-Luaces P, London HD, et al. Immunological, inflammatory and prothrombotic parameters in patients with COVID-19 treated with an anti-EGFR antibody. Immunol Lett. 2022;251-252:1-8. DOI: http://dx.doi.org/10.1016/j.imlet.2022.09.005
22. Samarakoon R, Overstreet JM, Higgins PJ. TGF-β signaling in tissue fibrosis: redox controls, target genes, and therapeutic opportunities. Cell Signaling. 2013 [accessed 01/12/2023];25(1):264-8. Available at: https://pubmed.ncbi.nlm.nih.gov/23063463/
23. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, et al. An atlas of mouse and human protein-coding transcriptome genes. Proc Natl Acad Sci USA. 2004 [accessed 01/12/2023];101(16):6062-7. Available at: https://pubmed.ncbi.nlm.nih.gov/15075390/
24. Kalinina O, Golovkin A, Zaikova E, Aquino A, Bezrukikh V, Melnik O, et al. Cytokine storm signature in patients with moderate and severe COVID-19. Int J Mol Sci. 2022 [accessed 01/12/2023];23(16):8879. Available at: https://pubmed.ncbi.nlm.nih.gov/36012146/
25. Meybosch S, De Monie A, Anné C, Bruyndonckx L, Jürgens A, De Winter BY, et al. Epidermal growth factor and its influencing variables in healthy children and adults. PLoS One. 2019 [accessed 01/12/2023];14(1):e0211212. Available at: https://pubmed.ncbi.nlm.nih.gov/30677083/
26. Perez Idania G, Haslen Hassiul CL, Adriana CP, Monzon Kalet L. Measurement of serum EGF levels, a methodological approach: learning what "low/high serum EGF concentration" means. Some clinical implications. J Mol Biomark Diagn. 2017 [accessed 01/12/2023];08(03). Available at: https://www.semanticscholar.org/paper/94218b9903985db99dbff799dbe656229e9caaec
27. Blood protein-EGF-The Human Protein Atlas. Proteinatlas.org [accessed 01/12/2023]. Available at: https://www.proteinatlas.org/ENSG00000138798-EGF/blood+protein
28. Madè A, Greco S, Vausort M, Miliotis M, Schordan E, Baksi S, et al. Association of peripheral blood miR-144 levels with COVID-19 severity and mortality. Science Rep. 2022 [accessed 01/12/2023];12(1). Available at: https://pubmed.ncbi.nlm.nih.gov/36414650/
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