Russian Medical Inquiry
(RMZh. Meditsinskoe Obozrenie) ISSN 2587-6821 (Print), 2686-9918 (Online)

Effect of obstructive sleep apnea-hypopnea syndrome 
on E-cadherin expression in esophageal epithelium

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DOI: 10.32364/2587-6821-2020-4-5-268-273

Yu.Ya. Shelkovich

Grodno State Medical University, Grodno, Republic of Belarus

Aim: to evaluate the effect of obstructive sleep apnea-hypopnea syndrome (OSAHS) on E-cadherin expression and epithelium histoarchitectonics of the lower third of the esophagus.

Patients and Methods: 108 patients were included in a cross-sectional comparative study. According to the results of somnology, a mild severity of OSAHS was diagnosed in 49 patients (group 1), an average severity — in 29 (group 2). Group 3 included 30 people without OSAHS. All patients underwent esophagogastroduodenoscopy with a biopsy of the lower third of the esophagus. Morphometrics of epithelial thickness, height of connective tissue papillae, and internuclear distances in all epithelial layers was performed. To assess the E-cadherin expression, immunohistochemistry was performed using monoclonal antibodies to E-cadherin.

Results: in contrast to the comparison group, patients with mild and moderate OSAHS were characterized by a higher epithelium thickness (273 (228; 372), 360 (312; 411),  186 (168; 192) μm, respectively, р1–3=0.000, р2–3=0.000), higher connective tissue papillae (108 (96; 120), 144 (120; 228), 72 (60; 84) μm, respectively, р1–3=0,001, р2–3=0,000), and larger internuclear distances in superficial layer (9 (7; 10), 8 (7; 9), 6 (5; 7) μm, respectively, р1–3=0.000, р2–3=0.002), spinous layer (8 (6; 9), 8 (7; 8), 6 (5; 7) μm, respectively, р1–3=0.000, р2–3=0.000), basal layer (4 (3; 5), 3 (3; 4), 2 (2; 3) μm, respectively, р1–3=0.000, р2–3=0,001) of epithelium. E-cadherin expression decreased in patients with both mild OSAHS (0.748 (0.623; 0.833) and 0.539 (0.263; 0.676), respectively, p=0.044) and moderate OSAHS (0.748 (0.623; 0.833) and 0.163 (0.026; 0.365), respectively, p=0.000) versus the comparison group. Correlations were found between respiratory monitoring indicators and E-cadherin expression in the esophageal epithelium.

Conclusion: OSAHS negatively affects the lining condition of the lower third of the esophagus, contributes to the loss of E-cadherin, which creates conditions for disorganization of epithelial tissue and increases the risk of precancerous diseases and esophageal cancer.

Keywords: obstructive sleep apnea-hypopnea syndrome, E-cadherin, esophageal epithelium, histoarchitectonics, epithelial-mesenchymal transition, intermittent hypoxia, apnea-hypopnea index.

For citation: Shelkovich Yu.Ya. Effect of obstructive sleep apnea-hypopnea syndrome on E-cadherin expression in esophageal epithelium. Russian Medical Inquiry. 2020;4(5):268–273. DOI: 10.32364/2587-6821-2020-4-5-268-273.



About the author:

Yulia Ya. Shelkovich — Assistant Professor of the 2nd Department of Internal Medicine, Grodno State Medical University: 80, Gorkogo str., Grodno, 230009, Republic of Belarus, ORCID iD 0000-0001-5942-3778.


Contact information: Yulia Ya. Shelkovich, e-mail: lazarilin@mail.ru. Financial Disclosure: the author has not a financial or property interest in any material or method mentioned. There is no conflict of interest. Received 28.08.2020, revised 11.09.2020, accepted 25.09.2020.

References
1. Lopatin A.S., Mel’nik S.M. Gastroesophageal reflux disease and pharyngolaryngeal reflux in patients with obstructive sleep apnea syndrome. Russian Journal of Evidence-based Gastroenterology. 2014;3(4):15–21 (in Russ.). DOI: 10.17116/dokgastro20143415-21.
2. Senaratna C.V., Perret J.L., Lodge C.J. et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev. 2017;34:70–81. DOI: 10.1016/j.smrv.2016.07.002.
3. Jara S.M., Phipps A.I., Maynard C. et al. The Association of Sleep Apnea and Cancer in Veterans. Otolaryngol Head Neck Surg. 2020;162(4):581–588. DOI: 10.1177/0194599819900487.
4. Chen C.Y., Hu J.M., Shen C.J. et al. Increased incidence of colorectal cancer with obstructive sleep apnea: a nationwide population-based cohort study. Sleep Med. 2020;66:15–20. DOI: 10.1016/j.sleep.2019.02.016.
5. Gao X.L., Jia Z.M., Zhao F.F. et al. Obstructive sleep apnea syndrome and causal relationship with female breast cancer: a mendelian randomization study. Aging (Albany NY). 2020;12(5):4082–4092. DOI: 10.18632/aging.102725.
6. Sillah A., Watson N.F., Schwartz S.M. et al. Sleep apnea and subsequent cancer incidence. Cancer Causes Control. 2018;29(10):987–994. DOI: 10.1007/s10552-018-1073-5.
7. Geramizadeh B., Salehzadeh A., Taghavi A. et al. Comparison of proliferative (Ki67) and cell adhesion (E-cadherin) markers between gastric intestinal metaplasia and Barrett’s esophagus. Indian J Gastroenterol. 2009;28(3):115–116. DOI: 10.1007/s12664-009-0040-1.
8. Daulagala A.C., Bridges M.C., Kourtidis A. E-cadherin beyond structure: a signaling hub in colon homeostasis and disease. Int J Mol Sci. 2019;20(11):1–17. DOI: 10.3390/ijms20112756.
9. Puchinskaya M.V. Epithelial-mesenchymal transition in health and disease. Archive of Pathology. 2015;77(1):75–83 (in Russ.). DOI: 10.17116/patol201577175-.
10. Shelkovich Y.Y. The Role of E-cadherin in the assessment of esophageal mucosal damage in patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(3):25–32 (in Russ.). DOI: 10.25298/2616-5546-2019-3-2-184-189.
11. Kasymova O.D. Diagnosis of obstructive sleep apnea in a general somatic hospital. J Clin Med Kaz. 2011;22,23 (3–4):12–14 (in Russ.).
12. Alekseeva O.V., Schnaider N.A., Demko I.V. et al. Obstructive sleep apnea/hypopnea syndrome of sleep: criteria of severity, pathogenesis, clinical manifestations and methods of diagnosis. Siberian Scientific Medical Journal. 2016;1:91–96 (in Russ.).
13. Shtabinskaja T.T., Basinskij V.A., Ljalikov S.A. et al. Colon Adenocarcinoma Angiogenesis. Grodno: GrGMU; 2018 (in Russ.).
14. Shelkovich Y.Y., Shishko V.I., Basinsky V.A. et al. E-cadherin expression in esophageal mucosa in patients with gastroesophageal reflux disease and/or obstructive sleep apnea/hypopnea syndrome. Hepatology and Gastroenterology. 2019;3(2):184–189 (in Russ.). DOI: 10.25298/2616-5546-2019-3-2-184-189.
15. Jing S.W., Wang Y.D., Kuroda M. et al. HIF-1α contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inhibiting E-cadherin and promoting MMP-2 expression. Acta Med Okayama. 2012;66(5):399–407.
16. Jing S.W., Wang Y.D., Kuroda M. et al. Hypoxia suppresses E-cadherin and enhances matrix metalloproteinase-2 expression favoring esophageal carcinoma migration and invasion via hypoxia inducible factor-1 alpha activation. Dis Esophagus. 2013;26(1):75–83. DOI: 10.1111/j.1442-2050.2011.01321.x.
17. Balabanovich T.I., Shyshko V.I., Shulika V.R. The impact of obstructive sleep apnea/hypopnea syndrome on tissue inhibitor of matrix metalloproteinase-1 and hypoxia inducible factor-1α levels in atrial fibrillation patients. Journal of the Grodno State Medical University. 2020;18(3):264–270 (in Russ.). DOI: 10.25298/2221-8785-2020-18-3-264-270.
18. Markin A.V., Martynenko T.I., Kostyuchenko G.I. et al. Cardiovascular risk factors in patients with obstructive sleep apnea syndrome. Clinician. 2014;1:15–20 (in Russ.).
19. Semenza G.L. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721–732. DOI:10.1038/nrc1187.
20. Zhong H., De Marzo A.M., Laughner E. et al. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their Metastasis. Cancer Res. 1999;59(22):5830–5835.
21. Talks K.L., Turley H., Gatter K.C. et al. The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. 2000;157(2):411–421. DOI: 10.1016/S0002-9440 (10) 64554-3.

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