LY6E level associated with smoking as risk for lung cancer patients susceptible to COVID-19

Studies revealed that cancer patients seemed more susceptible to COVID-19 and the clinical symptoms were serious. A recent study depicted that lymphocyte antigen 6 complex, locus E (LY6E) might inhibit coronavirus entry into cells by interfering with the membrane fusion process mediated through spike protein, and potently restricting the SARS-CoV-2 (Severe acute respiratory syndrome-associated coronavirus 2) infection. LY6E mRNA level in lung cancer was detected by publicly available datasets. Patient-specific features were used to analyze the potential factors that could affect LY6E level. Analysis of association between LY6E level and immune infiltration was also performed. In present study, it was found that smoker with lung adenocarcinoma showed lower LY6E level than non-smoker (p < 0.05). In LUSC (lung squamous cell carcinoma) patients, reformed smokers showed higher LY6E than smokers (p < 0.05). These results suggested that smoke can be a risk susceptible to COVID-19 in lung cancer patients. Further studies exhibited that LY6E was positively associated with immune cell infiltration in lung adenocarcinoma, indicating that LY6E may influence the infection severity of COVID-19 in lung cancer patients. In summary, smoke may downregulate LY6E level and exacerbate infection and deterioration of COVID-19 in lung cancer patients.

LY6E; Smoke; Lung cancer; Susceptibility; COVID-19

[1] Sidaway P. COVID-19 and cancer: what we know so far. Nature Reviews Clinical Oncology. 2020; 17: 336–336.

[2] Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020; 323: 1775–1776.

[3] Wang Q, Berger NA, Xu R. Analyses of risk, racial disparity, and outcomes among us patients with cancer and COVID-19 infection. JAMA Oncology. 2021; 7: 220.

[4] Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. The Lancet Oncology. 2020; 21: 335–337.

[5] Luo J, Rizvi H, Preeshagul IR, Egger JV, Hoyos D, Bandlamudi C, et al. COVID-19 in patients with lung cancer. Annals of Oncology. 2020; 31: 1386–1396.

Passaro A, Bestvina C, Velez Velez M, Garassino MC, Garon E, Peters S. Severity of COVID-19 in patients with lung cancer: evidence and challenges. Journal for ImmunoTherapy of Cancer. 2021; 9: e002266.

[7] Pathania AS, Prathipati P, Abdul BA, Chava S, Katta SS, Gupta SC, et al. COVID-19 and cancer comorbidity: therapeutic opportunities and challenges. Theranostics. 2021; 11: 731–753.

[8] Lee PY, Wang J, Parisini E, Dascher CC, Nigrovic PA. Ly6 family proteins in neutrophil biology. Journal of Leukocyte Biology. 2013; 94: 585–594.

[9] Godfrey DI, Masciantonio M, Tucek CL, Malin MA, Boyd RL, Hugo P. Thymic shared antigen-1. A novel thymocyte marker discriminating immature from mature thymocyte subsets. Journal of Immunology. 1992; 148: 2006–2011.

[10] Saitoh S, Kosugi A, Noda S, Yamamoto N, Ogata M, Minami Y, et al. Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2). Journal of Immunology. 1995; 155: 5574–5581.

[11] Pfaender S, Mar KB, Michailidis E, Kratzel A, Boys IN, V’Kovski P, et al. LY6E impairs coronavirus fusion and confers immune control of viral disease. Nature Microbiology. 2020; 5: 1330–1339.

[12] Nandi S, Roy H, Gummadi A, Saxena AK. Exploring spike protein as potential target of novel coronavirus and to inhibit the viability utilizing natural agents. Current Drug Targets. 2021; 22: 2006–2020.

[13] Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Coronaviruses. Methods in Molecular Biology. 2015; 1282: 1–23.

[14] Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. The Lancet Respiratory Medicine. 2020; 8: e46–e47.

[15] Barton LM, Duval EJ, Stroberg E, Ghosh S, Mukhopadhyay S. COVID-19 autopsies, Oklahoma, USA. American Journal of Clinical Pathology. 2020; 153: 725–733.

[16] Hu B, Huang S, Yin L. The cytokine storm and COVID‐19. Journal of Medical Virology. 2021; 93: 250–256.

[17] Nestler T, Dalvi P, Haidl F, Wittersheim M, von Brandenstein M, Paffenholz P, et al. Transcriptome analysis reveals upregulation of immune response pathways at the invasive tumour front of metastatic seminoma germ cell tumours. British Journal of Cancer. 2022; 126: 937–947.

[18] Strnadová K, Pfeiferová L, Přikryl P, Dvořánková B, Vlčák E, Frýdlová J, et al. Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts. Histochemistry and Cell Biology. 2022; 157: 153–172.

[19] Addeo A, Obeid M, Friedlaender A. COVID-19 and lung cancer: risks, mechanisms and treatment interactions. Journal for ImmunoTherapy of Cancer. 2020; 8: e000892.

[20] Robilotti EV, Babady NE, Mead PA, Rolling T, Perez-Johnston R, Bernardes M, et al. Determinants of COVID-19 disease severity in patients with cancer. Nature Medicine. 2020; 26: 1218–1223.

[21] Mar KB, Van Dyke MC, Lopez AH, Eitson JL, Fan W, Hanners NW, et al. LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2. bioRχiv. 2023. [Preprint].

[22] Zhao X, Zheng S, Chen D, Zheng M, Li X, Li G, et al. LY6E Restricts entry of human coronaviruses, including currently pandemic SARS-CoV-2. Journal of Virology. 2020; 94: e00562-20.

[23] Prior IA, Hood FE, Hartley JL. The frequency of Ras mutations in cancer. Cancer Research. 2020; 80: 2969–2974.

[24] Martin P, Leighl NB, Tsao M, Shepherd FA. KRAS mutations as prognostic and predictive markers in non-small cell lung cancer. Journal of Thoracic Oncology. 2013; 8: 530–542.

[25] Adderley H, Blackhall FH, Lindsay CR. KRAS-mutant non-small cell lung cancer: converging small molecules and immune checkpoint inhibition. EBioMedicine. 2019; 41: 711–716.