Cancer Research on Prevention and Treatment    2022, Vol. 49 Issue (06) : 586-592     DOI: 10.3971/j.issn.1000-8578.2022.21.1222
Expression of MAD2L1 in Lung Adenocarcinoma and Its Effect on Immune Microenvironment
LIU Yingbo1, LIU Xiaohong2, RU Meihua1, LI Jianqiang2
1. The Second Clinical Medical School of Shanxi Medical University, Taiyuan 030001, China; 2. Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, Taiyuan 030002, China
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Abstract Objective To investigate the expression of MAD2L1 in lung adenocarcinoma and its effect on the prognosis and immune microenvironment of patients. Methods The difference of MAD2L1 expression in lung adenocarcinoma tissue and normal lung tissue was analyzed by TCGA and GEO database. Survival analysis was carried out to evaluate the prognostic significance of MAD2L1 gene expression in lung adenocarcinoma patients. StarBase database was used to construct miRNA-MAD2L1 regulatory network of lung adenocarcinoma. The relation between the expression of MAD2L1 and immune cell infiltration in lung adenocarcinoma was analyzed by TIMER database. Results The expression of MAD2L1 was upregulated in lung adenocarcinoma, and the high expression of MAD2L1 was significantly correlated with pathological stage and lymph node metastasis of lung adenocarcinoma. The patients with high expression of MAD2L1 had a poor prognosis. miR-101-3p/MAD2L1 axis was identified as the most potential upstream regulation pathway of MAD2L1 in lung adenocarcinoma. The expression level of MAD2L1 was significantly correlated with tumor immune cell infiltration and immune checkpoint expression. Conclusion MAD2L1 is highly expressed in lung adenocarcinoma, which is related to poor prognosis and tumor immune infiltration. MAD2L1 can be used as a potential target for the treatment of lung adenocarcinoma.
Keywords MAD2L1      Lung adenocarcinoma      Prognosis      Immune infiltration      Immune microenvironment     
ZTFLH:  R734.2  
Fund:General Program of Shanxi Natural Science Foundation (No. 201901D111 391)
Issue Date: 16 June 2022
 Cite this article:   
. Expression of MAD2L1 in Lung Adenocarcinoma and Its Effect on Immune Microenvironment[J]. Cancer Research on Prevention and Treatment,2022, 49(06): 586-592.
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[1] Torre LA, Siegel RL, Jemal A. Lung Cancer Statistics[J]. Adv Exp
Med Biol, 2016, 893: 1-19.
[2] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics
2018: GLOBOCAN estimates of incidence and mortality
worldwide for 36 cancers in 1 85 countries[J]. CA Cancer J Clin,
2018, 68(6): 394-424.
[3] Eanes WF. New views on the selection acting on genetic
polymorphism in central metabolic genes[J]. Ann N Y Acad Sci,
2017, 1389(1): 108-123.
[4] Xu XH, Kou LC, Wang HM, et al. Genetic polymorphisms of
melatonin receptors 1 A and 1 B may result in disordered lipid
metabolism in obese patients with polycystic ovary syndrome[J].
Mol Med Rep, 2019, 19(3): 2220-2230.
[5] Luo C, Lei M, Zhang Y, et al. Systematic construction
and validation of an immune prognostic model for lung
adenocarcinoma[J]. J Cell Mol Med, 2020, 24(2): 1233-1244.
[6] Foijer F, Albacker LA, Bakker B, et al. Deletion of the MAD2L1 spindle assembly checkpoint gene is tolerated in mouse models
of acute T-cell lymphoma and hepatocellular carcinoma[J]. Elife,
2017, 6: e20873.
[7] Kim Y, Choi JW, Lee JH, et al. Spindle assembly checkpoint
MAD2 and CDC20 overexpr‍essions and cell-in-cell formation in
gastric cancer and its precursor lesions[J]. Hum Pathol, 2019, 85:
[8] Chandrashekar DS, Bashel B, Balasubramanya AH, et al.
UALCAN: A Portal for Facilitating Tumor Subgroup Gene
Expression and Survival Analyses[J]. Neoplasia, 2017, 1 9(8):
[9] Li T, Fan J, Wang B, et al. TIMER: A Web Server for
Comprehensive Analysis of Tumor-Infiltrating Immune Cells[J].
Cancer Res, 2017, 77(21): e108-e11 0.
[10] Leal-esteban LC, Fajas L. Cell cycle regulators in cancer cell
metabolism[J]. Biochim Biophys Acta Mol Basis Dis, 2020,
1866(5): 165715.
[11 ] Niwa M. A cell cycle checkpoint for the endoplasmic reticulum[J].
Biochim Biophys Acta Mol Cell Res, 2020, 1867(12): 11 8825.
[12] Alikhanyan K, Chen Y, Somogyi K, et al. Mad2 Induced
Aneuploidy Contributes to Eml4-Alk Driven Lung Cancer
by Generating an Immunosuppressive Environment[J].
Cancers(Basel), 2021, 13(23): 6027.
[13] Wenzel ES, Singh TK. Cell-cycle Checkpoints and Aneuploidy on
the Path to Cancer[J]. In vivo, 2018, 32(1): 1-5.
[14] Gay S. A novel function for the mitotic checkpoint protein Mad2p
in translation[J]. Mol Cell Oncol, 2018, 5(4): e1494949.
[15] Zhu XF, Yi M, He J, et al. Pathological significance of MAD2L1 in breast cancer: an immunohistochemical study and meta
analysis[J]. Int J Clin Exp Pathol, 2017, 10(9): 9190-9201.
[16] Li Y, Bai W, Zhang J. MiR-200c-5p suppresses proliferation
and metastasis of human hepatocellular carcinoma (HCC) via
suppressing MAD2L1[J]. Biomed Pharmacother, 2017, 92:
[17] Wang Y, Wang F, He J, et al. miR-30a-3p Targets MAD2L1 and
Regulates Proliferation of Gastric Cancer Cells[J]. Onco Targets
Ther, 2019, 12: 11 313-11 324.
[18] Lin X, Zhou M, Xu Z, et al. Bioinformatics study on genes related
to a high-risk postoperative recurrence of lung adenocarcinoma[J].
Sci Prog, 2021, 104(3): 368504211 018053.
[19] Shi YX, Zhu T, Zou T, et al. Prognostic and predictive values of
CDK1 and MAD2L1 in lung adenocarcinoma[J]. Oncotarget,
2016, 7(51): 85235-85243.
[20] Meng X, Sun Y, Liu S, et al. miR-101-3p sensitizes lung
adenocarcinoma cells to irradiation via targeting BIRC5[J]. Oncol
Lett, 2021, 21(4): 282.
[21] Liu SH, Hsu KW, Lai YL, et al. Systematic identification of
clinically relevant miRNAs for potential miRNA-based therapy in
lung adenocarcinoma[J]. Mol Ther Nucleic Acid, 2021, 25: 1-10.
[22] Waniczek D, Lorenc Z, ?nietura M, et al. Tumor-Associated
Macrophages and Regulatory T Cells Infiltration and the
Clinical Outcome in Colorectal Cancer[J]. Arch Immunol Ther
Exp(Warsz), 2017, 65(5): 445-454.
[23] Zhang H, Liu H, Shen Z, et al. Tumor-infiltrating Neutrophils
is Prognostic and Predictive for Postoperative Adjuvant
Chemotherapy Benefit in Patients With Gastric Cancer[J]. Ann
Surgery, 2018, 267(2): 311 -318.
[24] Lyu L, Yao J, Wang M, et al. Overexpressed Pseudogene HLADPB2
Promotes Tumor Immune Infiltrates by Regulating HLADPB1 and
Indicates a Better Prognosis in Breast Cancer[J]. Front
Oncol, 2020, 10: 1245.
[25] Chae YK, Arya A, Iams W, et al. Current landscape and future of
dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in
cancer; lessons learned from clinical trials with melanoma and
non-small cell lung cancer (NSCLC)[J]. J Immunother Cancer,
2018, 6(1): 39.
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