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Clinical Significance and Prognostic Value of the Expression of LAG-3 and FGL1 in Esophageal Squamous Cell Carcinoma

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In this retrospective study, we analyzed the expression of lymphocyte activating gene 3 (LAG-3) and fibrinogen-like protein 1 (FGP1) mRNA and the corresponding proteins in 78 patients with esophageal squamous cell carcinoma (ESCC) to evaluate the clinical significance and prognostic value. mRNA and protein expression were analyzed by reverse transcription PCR and Western blotting, respectively. The expression of LAG-3 and FGL1 mRNA and the corresponding proteins in tumor tissues were significantly increased in comparison with the normal esophageal mucosa. The overexpression of LAG-3 significantly correlated with the content of tumor-infiltrating lymphocytes (TILs), tumor differentiation, and TNM stage. The overexpression of FGL1 also significantly correlated with TILs, TNM stage, and lymph node metastasis. Kaplan—Meier survival analysis showed that tumor diameter, TNM stage, lymph node metastasis, LAG-3 and FGL1 protein expression were related to the progression-free survival (p<0.05). Multivariate Cox regression showed that the level of FGL1 and TNM stage were independent prognostic factors of progression-free survival. We speculated that the tumor microenvironment of ESCC induces immunosuppression due to up-regulated expression of LAG-3 and FGL1 in the tumor tissues, which promotes tumor growth.

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References

  1. Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, Yang Z, Li H, Zou X, He J. Cancer incidence and mortality in China, 2014. Chin. J. Cancer Res. 2018;30(1):1-12. https://doi.org/10.21147/j.issn.1000-9604.2018.01.01

  2. Lohan-Codeço M, Barambo-Wagner ML, Nasciutti LE, Ribeiro Pinto LF, Meireles Da Costa N, Palumbo A Jr. Molecular mechanisms associated with chemoresistance in esophageal cancer. Cell. Mol. Life Sci. 2022;79(2):116. https://doi.org/10.1007/s00018-022-04131-6

  3. Andrews LP, Marciscano AE, Drake CG, Vignali DA. LAG3 (CD223) as a cancer immunotherapy target. Immunol. Rev. 2017;276(1):80-96. https://doi.org/10.1111/imr.12519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tassi E, Grazia G, Vegetti C, Bersani I, Bertolini G, Molla A, Baldassari P, Andriani F, Roz L, Sozzi G, Pastorino U, Mortarini R, Anichini A. Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non-Small Cell Lung Cancer. Cancer Res. 2017;77(4):851-861. https://doi.org/10.1158/0008-5472.CAN-16-1387

    Article  CAS  PubMed  Google Scholar 

  5. Shapiro M, Herishanu Y, Katz BZ, Dezorella N, Sun C, Kay S, Polliack A, Avivi I, Wiestner A, Perry C. Lymphocyte activation gene 3: a novel therapeutic target in chronic lymphocytic leukemia. Haematologica. 2017;102(5):874-882. https://doi.org/10.3324/haematol.2016.148965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Deng WW, Mao L, Yu GT, Bu LL, Ma SR, Liu B, Gutkind JS, Kulkarni AB, Zhang WF, Sun ZJ. LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma. Oncoimmunology. 2016;5(11):e1239005. https://doi.org/10.1080/2162402X.2016.1239005

  7. Li CY, Cao CZ, Xu WX, Cao MM, Yang F, Dong L, Yu M, Zhan YQ, Gao YB, Li W, Wang ZD, Ge CH, Wang QM, Peng RY, Yang XM. Recombinant human hepassocin stimulates proliferation of hepatocytes in vivo and improves survival in rats with fulminant hepatic failure. Gut. 2010;59(6):817-826. https://doi.org/10.1136/gut.2008.171124

    Article  CAS  PubMed  Google Scholar 

  8. Demchev V, Malana G, Vangala D, Stoll J, Desai A, Kang HW, Li Y, Nayeb-Hashemi H, Niepel M, Cohen DE, Ukomadu C. Targeted deletion of fibrinogen like protein 1 reveals a novel role in energy substrate utilization. PLoS One. 2013;8(3):e58084. https://doi.org/10.1371/journal.pone.0058084

  9. Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, Zheng L, Zhou T, Badri T, Yao S, Zhu S, Boto A, Sznol M, Melero I, Vignali DAA, Schalper K, Chen L. Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell. 2019;176(1-2):334-347.e12. https://doi.org/10.1016/j.cell.2018.11.010

    Article  CAS  PubMed  Google Scholar 

  10. Kojima YA, Wang X, Sun H, Compton F, Covinsky M, Zhang S. Reproducible evaluation of tumor-infiltrating lymphocytes (TIL) using the recommendations of International TIL Working Group 2014. Ann. Diagn. Pathol. 2018;35:77-79. https://doi.org/10.1016/j.anndiagpath.2018.05.007

    Article  PubMed  Google Scholar 

  11. Chocarro L, Blanco E, Zuazo M, Arasanz H, Bocanegra A, Fernández-Rubio L, Morente P, Fernández-Hinojal G, Echaide M, Garnica M, Ramos P, Vera R, Kochan G, Escors D. Understanding LAG-3 Signaling. Int. J. Mol. Sci. 2021;22(10):5282. https://doi.org/10.3390/ijms22105282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Y. Liu.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 174, No. 12, pp. 750-755, December, 2022

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Yao, X.M., Zhang, F.H. & Liu, Y. Clinical Significance and Prognostic Value of the Expression of LAG-3 and FGL1 in Esophageal Squamous Cell Carcinoma. Bull Exp Biol Med 174, 774–778 (2023). https://doi.org/10.1007/s10517-023-05796-0

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  • DOI: https://doi.org/10.1007/s10517-023-05796-0

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