Research progress of angiotensin converting enzyme 2 co-expression in non-small cell lung cancer and SARS-CoV-2_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

BAI Xiangdou ¹ , ZENG Weiqiang ¹ , CUI Baiqiang ¹ , WANG Bing ¹ , YANG Ning ¹ , HE Xiaoyang ¹ , ZHANG Siyuan ¹ , JIN Dacheng ² ,  GOU Yunjiu ¹

1. The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou, 730000, P. R. China;
2. Department of Thoracic Surgery, The Gansu Provincial Hospital, Lanzhou, 730000, P. R. China;

Corresponding author：

GOU Yunjiu, Email: gouyunjiu@163.com

Keywords：

Non-small cell lung cancer; angiotensin converting enzyme 2 (ACE2); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Spike protein; corona virus disease 2019 (COVID-19); review

DOI：

10.7507/1007-4848.202105077

Video：

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Since the first case of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019, the virus has spread rapidly around the world and has become a global public health problem. In the process of this virus epidemic, compared with the general population, cancer patients are considered to be highly susceptible people, especially the lung cancer patients. Some studies have shown that angiotensin converting enzyme 2 (ACE2) may be the pathway for SARS-CoV-2 to infect the host. At the same time, ACE2 is often abnormally expressed in non-small cell lung cancer. Therefore, understanding the respective mechanisms of ACE2 in COVID-19 and non-small cell lung cancer has extremely important reference value for the study of vaccines and therapeutic drugs, and also provides meaningful guidance for the protection of patients with lung cancer during the epidemic. This article reviews the possible invasive mechanism of ACE2 in SARS-CoV-2 and its abnormal expression in non-small cell lung cancer.

Citation： BAI Xiangdou, ZENG Weiqiang, CUI Baiqiang, WANG Bing, YANG Ning, HE Xiaoyang, ZHANG Siyuan, JIN Dacheng, GOU Yunjiu. Research progress of angiotensin converting enzyme 2 co-expression in non-small cell lung cancer and SARS-CoV-2. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(5): 773-778. doi: 10.7507/1007-4848.202105077 Copy

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2.	Corso CR, Mulinari Turin de Oliveira N, Maria-Ferreira D. Susceptibility to SARS-CoV-2 infection in patients undergoing chemotherapy and radiation therapy. J Infect Public Health, 2021, 14(6): 766-771.
3.	Ansari RM, Baker P. Identifying the predictors of COVID-19 infection outcomes and development of prediction models. J Infect Public Health, 2021, 14(6): 751-756.
4.	Boglione L, Olivieri C, Rostagno R, et al. Role of the early short-course corticosteroids treatment in ARDS caused by COVID-19: A single-center, retrospective analysis. Adv Med Sci, 2021, 66(2): 262-268.
5.	Maniscalco M, Fuschillo S, Ambrosino P, et al. Preexisting cardiorespiratory comorbidity does not preclude the success of multidisciplinary rehabilitation in post-COVID-19 patients. Respir Med, 2021, 184: 106470.
6.	Haeusler KG, Kirchhof P, Kunze C, et al. Systematic monitoring for detection of atrial fibrillation in patients with acute ischaemic stroke (MonDAFIS): A randomised, open-label, multicentre study. Lancet Neurol, 2021, 20(6): 426-436.
7.	Krasnow MR, Litt HK, Lehmann CJ, et al. Cancer, transplant, and immunocompromising conditions were not significantly associated with severe illness or death in hospitalized COVID-19 patients. J Clin Virol, 2021, 140: 104850.
8.	Piñero P, Marco De La Calle FM, Horndler L, et al. Flow cytometry detection of sustained humoral immune response (IgG+IgA) against native spike glycoprotein in asymptomatic/mild SARS-CoV-2 infection. Sci Rep, 2021, 11(1): 10716.
9.	王文辰, 夏彦明, 朱建飞, 等. 血管紧张素转换酶 2 在人类高致病性冠状病毒肺炎中作用的研究进展. 中国胸心血管外科临床杂志, 2020, 27(5): 588-596.
10.	Acharya A, Lynch DL, Pavlova A, et al. ACE2 glycans preferentially interact with SARS-CoV-2 over SARS-CoV. Chem Commun (Camb), 2021, 57(48): 5949-5952.
11.	SeyedAlinaghi S, Mehrtak M, MohsseniPour M, et al. Genetic susceptibility of COVID-19: A systematic review of current evidence. Eur J Med Res, 2021, 26(1): 46.
12.	Calò LA, Rigato M, Sgarabotto L, et al. ACE2 and SARS-CoV-2 infection risk: Insights from patients with two rare genetic tubulopathies, Gitelman's and Bartter's Syndromes. Front Med (Lausanne), 2021, 8: 647319.
13.	Kim KH, Choi BG, Rha SW, et al. Impact of renin angiotensin system inhibitor on 3-year clinical outcomes in acute myocardial infarction patients with preserved left ventricular systolic function: A prospective cohort study from Korea Acute Myocardial Infarction Registry (KAMIR). BMC Cardiovasc Disord, 2021, 21(1): 251.
14.	Marazuela M, Giustina A, Puig-Domingo M. Endocrine and metabolic aspects of the COVID-19 pandemic. Rev Endocr Metab Disord, 2020, 21(4): 495-507.
15.	Rodriguez-Perez AI, Labandeira CM, Pedrosa MA, et al. Autoantibodies against ACE2 and angiotensin type-1 receptors increase severity of COVID-19. J Autoimmun, 2021, 122: 102683.
16.	Ozbalci D. A tale of two diseases: Sarcoidosis, COVID-19 and new therapeutic options with dual RAS inhibition and tetanus-diphtheria vaccine. Med Hypotheses, 2021, 152: 110619.
17.	Sackin H. Hypothesis for renin-angiotensin inhibitor mitigation of COVID-19. Med Hypotheses, 2021, 152: 110609.
18.	Wehbe Z, Hammoud SH, Yassine HM, et al. Molecular and biological mechanisms underlying gender differences in COVID-19 severity and mortality. Front Immunol, 2021, 12: 659339.
19.	Raghav PK, Kalyanaraman K, Kumar D. Human cell receptors: Potential drug targets to combat COVID-19. Amino Acids, 2021, 53(6): 813-842.
20.	Herman-Edelstein M, Guetta T, Barnea A, et al. Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system. Cardiovasc Diabetol, 2021, 20(1): 90.
21.	Fang L, Zhao W, Ye B, et al. Combination of immune checkpoint inhibitors and anti-angiogenic agents in brain metastases from non-small cell lung cancer. Front Oncol, 2021, 11: 670313.
22.	Simko F, Baka T. Angiotensin-converting enzyme inhibitors and angiotensin Ⅱ receptor blockers: Potential allies in the COVID-19 pandemic instead of a threat? Clin Sci (Lond), 2021, 135(8): 1009-1014.
23.	Zhao M, Wang R, Yu Y, et al. Efficacy and safety of angiotensin-converting enzyme inhibitor in combination with angiotensin-receptor blocker in chronic kidney disease based on dose: A systematic review and meta-analysis. Front Pharmacol, 2021, 12: 638611.
24.	Yang LJ, Chen RH, Hamdoun S, et al. Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding. Phytomedicine, 2021, 87: 153591.
25.	Lozahic C, Maddock H, Sandhu H. Anti-cancer therapy leads to increased cardiovascular susceptibility to COVID-19. Front Cardiovasc Med, 2021, 8: 634291.
26.	Cheng Q, Zhou L, Zhou J, et al. ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC. Oncol Rep, 2016, 36(3): 1403-1410.
27.	Feng Y, Wan H, Liu J, et al. The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer. Oncol Rep, 2010, 23(4): 941-948.
28.	Górecki I, Rak B. The role of microRNAs in epithelial to mesenchymal transition and cancers; focusing on mir-200 family. Cancer Treat Res Commun, 2021, 28: 100385.
29.	Qian YR, Guo Y, Wan HY, et al. Angiotensin-converting enzyme 2 attenuates the metastasis of non-small cell lung cancer through inhibition of epithelial-mesenchymal transition. Oncol Rep, 2013, 29(6): 2408-2414.
30.	Monari C, Sagnelli C, Maggi P, et al. More severe COVID-19 in patients with active cancer: Results of a multicenter cohort study. Front Oncol, 2021, 11: 662746.
31.	Zong Z, Wei Y, Ren J, et al. The intersection of COVID-19 and cancer: Signaling pathways and treatment implications. Mol Cancer, 2021, 20(1): 76.
32.	Keewan E, Beg S, Naser SA. Anti-TNF-α agents modulate SARS-CoV-2 receptors and increase the risk of infection through Notch-1 signaling. Front Immunol, 2021, 12: 641295.
33.	Mahmood TB, Chowdhury AS, Hossain MU, et al. Evaluation of the susceptibility and fatality of lung cancer patients towards the COVID-19 infection: A systemic approach through analyzing the ACE2, CXCL10 and their co-expressed genes. Curr Res Microb Sci, 2021, 2: 100022.
34.	Ren P, Gong C, Ma S. Evaluation of COVID-19 based on ACE2 expression in normal and cancer patients. Open Med (Wars), 2020, 15(1): 613-622.
35.	Zhang H, Quek K, Chen R, et al. Expression of the SAR2-CoV-2 receptor ACE2 reveals the susceptibility of COVID-19 in non-small cell lung cancer. J Cancer, 2020, 11(18): 5289-5292.
36.	Lu L, Liu X, Jin R, et al. Potential roles of the renin-angiotensin system in the pathogenesis and treatment of COVID-19. Biomed Res Int, 2020, 2020: 7520746.
37.	Malkani N, Rashid MU. SARS-COV-2 infection and lung tumor microenvironment. Mol Biol Rep, 2021, 48(2): 1925-1934.
38.	Singh MK, Mobeen A, Chandra A, et al. A meta-analysis of comorbidities in COVID-19: Which diseases increase the susceptibility of SARS-CoV-2 infection? Comput Biol Med, 2021, 130: 104219.
39.	de Loyola MB, Dos Reis TTA, de Oliveira GXLM, et al. Alpha-1-antitrypsin: A possible host protective factor against COVID-19. Rev Med Virol, 2021, 31(2): e2157.
40.	Guney C, Akar F. Epithelial and endothelial expressions of ACE2: SARS-CoV-2 entry routes. J Pharm Pharm Sci, 2021, 24: 84-93.
41.	Viveiros A, Rasmuson J, Vu J, et al. Sex differences in COVID-19: Candidate pathways, genetics of ACE2, and sex hormones. Am J Physiol Heart Circ Physiol, 2021, 320(1): H296-H304.
42.	Abassi Z, Higazi AAR, Kinaneh S, et al. ACE2, COVID-19 infection, inflammation, and coagulopathy: Missing pieces in the puzzle. Front Physiol, 2020, 11: 574753.
43.	Latil M, Camelo S, Veillet S, et al. Developing new drugs that activate the protective arm of the renin-angiotensin system as a potential treatment for respiratory failure in COVID-19 patients. Drug Discov Today, 2021, 26(5): 1311-1318.
44.	Pironti G, Andersson DC, Lund LH. Mechanistic and therapeutic implications of extracellular vesicles as a potential link between COVID-19 and cardiovascular disease manifestations. Front Cell Dev Biol, 2021, 9: 640723.
45.	Bobkova NV. The balance between two branches of RAS can protect from severe COVID-19 course. Biochem (Mosc) Suppl Ser A Membr Cell Biol, 2021, 15(1): 36-51.
46.	Oz M, Lorke DE, Kabbani N. A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor. Pharmacol Ther, 2021, 221: 107750.

1. Wang MK, Yue HY, Cai J, et al. COVID-19 and the digestive system: A comprehensive review. World J Clin Cases, 2021, 9(16): 3796-3813.
2. Corso CR, Mulinari Turin de Oliveira N, Maria-Ferreira D. Susceptibility to SARS-CoV-2 infection in patients undergoing chemotherapy and radiation therapy. J Infect Public Health, 2021, 14(6): 766-771.
3. Ansari RM, Baker P. Identifying the predictors of COVID-19 infection outcomes and development of prediction models. J Infect Public Health, 2021, 14(6): 751-756.
4. Boglione L, Olivieri C, Rostagno R, et al. Role of the early short-course corticosteroids treatment in ARDS caused by COVID-19: A single-center, retrospective analysis. Adv Med Sci, 2021, 66(2): 262-268.
5. Maniscalco M, Fuschillo S, Ambrosino P, et al. Preexisting cardiorespiratory comorbidity does not preclude the success of multidisciplinary rehabilitation in post-COVID-19 patients. Respir Med, 2021, 184: 106470.
6. Haeusler KG, Kirchhof P, Kunze C, et al. Systematic monitoring for detection of atrial fibrillation in patients with acute ischaemic stroke (MonDAFIS): A randomised, open-label, multicentre study. Lancet Neurol, 2021, 20(6): 426-436.
7. Krasnow MR, Litt HK, Lehmann CJ, et al. Cancer, transplant, and immunocompromising conditions were not significantly associated with severe illness or death in hospitalized COVID-19 patients. J Clin Virol, 2021, 140: 104850.
8. Piñero P, Marco De La Calle FM, Horndler L, et al. Flow cytometry detection of sustained humoral immune response (IgG+IgA) against native spike glycoprotein in asymptomatic/mild SARS-CoV-2 infection. Sci Rep, 2021, 11(1): 10716.
9. 王文辰, 夏彦明, 朱建飞, 等. 血管紧张素转换酶 2 在人类高致病性冠状病毒肺炎中作用的研究进展. 中国胸心血管外科临床杂志, 2020, 27(5): 588-596.
10. Acharya A, Lynch DL, Pavlova A, et al. ACE2 glycans preferentially interact with SARS-CoV-2 over SARS-CoV. Chem Commun (Camb), 2021, 57(48): 5949-5952.
11. SeyedAlinaghi S, Mehrtak M, MohsseniPour M, et al. Genetic susceptibility of COVID-19: A systematic review of current evidence. Eur J Med Res, 2021, 26(1): 46.
12. Calò LA, Rigato M, Sgarabotto L, et al. ACE2 and SARS-CoV-2 infection risk: Insights from patients with two rare genetic tubulopathies, Gitelman's and Bartter's Syndromes. Front Med (Lausanne), 2021, 8: 647319.
13. Kim KH, Choi BG, Rha SW, et al. Impact of renin angiotensin system inhibitor on 3-year clinical outcomes in acute myocardial infarction patients with preserved left ventricular systolic function: A prospective cohort study from Korea Acute Myocardial Infarction Registry (KAMIR). BMC Cardiovasc Disord, 2021, 21(1): 251.
14. Marazuela M, Giustina A, Puig-Domingo M. Endocrine and metabolic aspects of the COVID-19 pandemic. Rev Endocr Metab Disord, 2020, 21(4): 495-507.
15. Rodriguez-Perez AI, Labandeira CM, Pedrosa MA, et al. Autoantibodies against ACE2 and angiotensin type-1 receptors increase severity of COVID-19. J Autoimmun, 2021, 122: 102683.
16. Ozbalci D. A tale of two diseases: Sarcoidosis, COVID-19 and new therapeutic options with dual RAS inhibition and tetanus-diphtheria vaccine. Med Hypotheses, 2021, 152: 110619.
17. Sackin H. Hypothesis for renin-angiotensin inhibitor mitigation of COVID-19. Med Hypotheses, 2021, 152: 110609.
18. Wehbe Z, Hammoud SH, Yassine HM, et al. Molecular and biological mechanisms underlying gender differences in COVID-19 severity and mortality. Front Immunol, 2021, 12: 659339.
19. Raghav PK, Kalyanaraman K, Kumar D. Human cell receptors: Potential drug targets to combat COVID-19. Amino Acids, 2021, 53(6): 813-842.
20. Herman-Edelstein M, Guetta T, Barnea A, et al. Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system. Cardiovasc Diabetol, 2021, 20(1): 90.
21. Fang L, Zhao W, Ye B, et al. Combination of immune checkpoint inhibitors and anti-angiogenic agents in brain metastases from non-small cell lung cancer. Front Oncol, 2021, 11: 670313.
22. Simko F, Baka T. Angiotensin-converting enzyme inhibitors and angiotensin Ⅱ receptor blockers: Potential allies in the COVID-19 pandemic instead of a threat? Clin Sci (Lond), 2021, 135(8): 1009-1014.
23. Zhao M, Wang R, Yu Y, et al. Efficacy and safety of angiotensin-converting enzyme inhibitor in combination with angiotensin-receptor blocker in chronic kidney disease based on dose: A systematic review and meta-analysis. Front Pharmacol, 2021, 12: 638611.
24. Yang LJ, Chen RH, Hamdoun S, et al. Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding. Phytomedicine, 2021, 87: 153591.
25. Lozahic C, Maddock H, Sandhu H. Anti-cancer therapy leads to increased cardiovascular susceptibility to COVID-19. Front Cardiovasc Med, 2021, 8: 634291.
26. Cheng Q, Zhou L, Zhou J, et al. ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC. Oncol Rep, 2016, 36(3): 1403-1410.
27. Feng Y, Wan H, Liu J, et al. The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer. Oncol Rep, 2010, 23(4): 941-948.
28. Górecki I, Rak B. The role of microRNAs in epithelial to mesenchymal transition and cancers; focusing on mir-200 family. Cancer Treat Res Commun, 2021, 28: 100385.
29. Qian YR, Guo Y, Wan HY, et al. Angiotensin-converting enzyme 2 attenuates the metastasis of non-small cell lung cancer through inhibition of epithelial-mesenchymal transition. Oncol Rep, 2013, 29(6): 2408-2414.
30. Monari C, Sagnelli C, Maggi P, et al. More severe COVID-19 in patients with active cancer: Results of a multicenter cohort study. Front Oncol, 2021, 11: 662746.
31. Zong Z, Wei Y, Ren J, et al. The intersection of COVID-19 and cancer: Signaling pathways and treatment implications. Mol Cancer, 2021, 20(1): 76.
32. Keewan E, Beg S, Naser SA. Anti-TNF-α agents modulate SARS-CoV-2 receptors and increase the risk of infection through Notch-1 signaling. Front Immunol, 2021, 12: 641295.
33. Mahmood TB, Chowdhury AS, Hossain MU, et al. Evaluation of the susceptibility and fatality of lung cancer patients towards the COVID-19 infection: A systemic approach through analyzing the ACE2, CXCL10 and their co-expressed genes. Curr Res Microb Sci, 2021, 2: 100022.
34. Ren P, Gong C, Ma S. Evaluation of COVID-19 based on ACE2 expression in normal and cancer patients. Open Med (Wars), 2020, 15(1): 613-622.
35. Zhang H, Quek K, Chen R, et al. Expression of the SAR2-CoV-2 receptor ACE2 reveals the susceptibility of COVID-19 in non-small cell lung cancer. J Cancer, 2020, 11(18): 5289-5292.
36. Lu L, Liu X, Jin R, et al. Potential roles of the renin-angiotensin system in the pathogenesis and treatment of COVID-19. Biomed Res Int, 2020, 2020: 7520746.
37. Malkani N, Rashid MU. SARS-COV-2 infection and lung tumor microenvironment. Mol Biol Rep, 2021, 48(2): 1925-1934.
38. Singh MK, Mobeen A, Chandra A, et al. A meta-analysis of comorbidities in COVID-19: Which diseases increase the susceptibility of SARS-CoV-2 infection? Comput Biol Med, 2021, 130: 104219.
39. de Loyola MB, Dos Reis TTA, de Oliveira GXLM, et al. Alpha-1-antitrypsin: A possible host protective factor against COVID-19. Rev Med Virol, 2021, 31(2): e2157.
40. Guney C, Akar F. Epithelial and endothelial expressions of ACE2: SARS-CoV-2 entry routes. J Pharm Pharm Sci, 2021, 24: 84-93.
41. Viveiros A, Rasmuson J, Vu J, et al. Sex differences in COVID-19: Candidate pathways, genetics of ACE2, and sex hormones. Am J Physiol Heart Circ Physiol, 2021, 320(1): H296-H304.
42. Abassi Z, Higazi AAR, Kinaneh S, et al. ACE2, COVID-19 infection, inflammation, and coagulopathy: Missing pieces in the puzzle. Front Physiol, 2020, 11: 574753.
43. Latil M, Camelo S, Veillet S, et al. Developing new drugs that activate the protective arm of the renin-angiotensin system as a potential treatment for respiratory failure in COVID-19 patients. Drug Discov Today, 2021, 26(5): 1311-1318.
44. Pironti G, Andersson DC, Lund LH. Mechanistic and therapeutic implications of extracellular vesicles as a potential link between COVID-19 and cardiovascular disease manifestations. Front Cell Dev Biol, 2021, 9: 640723.
45. Bobkova NV. The balance between two branches of RAS can protect from severe COVID-19 course. Biochem (Mosc) Suppl Ser A Membr Cell Biol, 2021, 15(1): 36-51.
46. Oz M, Lorke DE, Kabbani N. A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor. Pharmacol Ther, 2021, 221: 107750.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research progress of angiotensin converting enzyme 2 co-expression in non-small cell lung cancer and SARS-CoV-2

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