Research article Special Issues

Identification of novel immunomodulators in lung squamous cell carcinoma based on transcriptomic data

  • These authors contributed equally to this work
  • Received: 03 September 2021 Accepted: 24 November 2021 Published: 20 December 2021
  • Cells in the tumor microenvironment are well known for their role in cancer development and prognosis. The processes of genetic changes and possible remodeling in the tumor microenvironment of lung squamous cell carcinoma, on the other hand, are mainly unclear. In this investigation, 1164 immunological differentially expressed genes (DEGs) were shown to have predictive significance. A prognostic model with high prediction accuracy was constructed using these genes and survival data. There were 1020 upregulated genes and 144 downregulated genes found, with 57 genes found to be important in the development of LUSC. We used least absolute shrinkage and selection operator (LASSO) regression analysis to determine the risk profiles of 9 genes based on the expression values of 57 prognosis-related genes. The AUCs of the developed prognostic model for predicting patient survival at 1, 3, and 5 years were 0.66, 0.61, and 0.63, respectively, based on the training data. For immune-correlation analysis in this survival model, we chose IGLC7, which was seen to predict patient survival with high accuracy. The effects on immune cells and synergistic effects with other immunomodulators were then investigated. We discovered that IGLC7 is involved in immune response and inflammatory activity using gene ontology analysis and genomic sequence variance analysis (GSVA), with a potential effect, especially on B cells and T cells. In conclusion, IGLC7 expression levels are related to the malignancy of LUSC based on the constructed prognostic model and can thus be a therapeutic target for patients with LUSC. Furthermore, IGLC7 may work in concert with other immune checkpoint members to regulate the immune microenvironment of LUSC. These discoveries might lead to a fresh understanding of the complicated interactions between cancer cells and the tumor microenvironment, particularly the population of immune cells, and a novel approach to future immunotherapeutic treatments for patients with LUSC.

    Citation: Xin Lin, Xingyuan Li, Binqiang Ma, Lihua Hang. Identification of novel immunomodulators in lung squamous cell carcinoma based on transcriptomic data[J]. Mathematical Biosciences and Engineering, 2022, 19(2): 1843-1860. doi: 10.3934/mbe.2022086

    Related Papers:

  • Cells in the tumor microenvironment are well known for their role in cancer development and prognosis. The processes of genetic changes and possible remodeling in the tumor microenvironment of lung squamous cell carcinoma, on the other hand, are mainly unclear. In this investigation, 1164 immunological differentially expressed genes (DEGs) were shown to have predictive significance. A prognostic model with high prediction accuracy was constructed using these genes and survival data. There were 1020 upregulated genes and 144 downregulated genes found, with 57 genes found to be important in the development of LUSC. We used least absolute shrinkage and selection operator (LASSO) regression analysis to determine the risk profiles of 9 genes based on the expression values of 57 prognosis-related genes. The AUCs of the developed prognostic model for predicting patient survival at 1, 3, and 5 years were 0.66, 0.61, and 0.63, respectively, based on the training data. For immune-correlation analysis in this survival model, we chose IGLC7, which was seen to predict patient survival with high accuracy. The effects on immune cells and synergistic effects with other immunomodulators were then investigated. We discovered that IGLC7 is involved in immune response and inflammatory activity using gene ontology analysis and genomic sequence variance analysis (GSVA), with a potential effect, especially on B cells and T cells. In conclusion, IGLC7 expression levels are related to the malignancy of LUSC based on the constructed prognostic model and can thus be a therapeutic target for patients with LUSC. Furthermore, IGLC7 may work in concert with other immune checkpoint members to regulate the immune microenvironment of LUSC. These discoveries might lead to a fresh understanding of the complicated interactions between cancer cells and the tumor microenvironment, particularly the population of immune cells, and a novel approach to future immunotherapeutic treatments for patients with LUSC.



    加载中


    [1] L. Gao, Y. N. Guo, J. H. Zeng, F. C. Ma, J. Luo, H. W. Zhu, et al., The expression, significance and function of cancer susceptibility candidate 9 in lung squamous cell carcinoma: A bioinformatics and in vitro investigation, Int. J. Oncol., 54 (2019), 1651-1664. doi: 10.3892/ijo.2019.4758. doi: 10.3892/ijo.2019.4758
    [2] J. Xu, Y. Shu, T. Xu, W. Zhu, T. Qiu, J. Li, et al., Microarray expression profiling and bioinformatics analysis of circular RNA expression in lung squamous cell carcinoma, Am. J. Transl. Res., 10 (2018), 771-783. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883118/.
    [3] H. Lemjabbar-Alaoui, O. U. Hassan, Y. W. Yang, P. Buchanan, Lung cancer: Biology and treatment options, Biochim. Biophys. Acta, 1856 (2015), 189-210. doi: 10.1016/j.bbcan.2015.08.002. doi: 10.1016/j.bbcan.2015.08.002
    [4] C. A. Granville, P. A. Dennis, An overview of lung cancer genomics and proteomics, Am. J. Respir. Cell Mol. Biol., 32 (2005), 169-76. doi: 10.1165/rcmb.F290. doi: 10.1165/rcmb.F290
    [5] D. Morgensztern, S. Waqar, J. Subramanian, F. Gao, R. Govindan, Improving survival for stage IV non-small cell lung cancer: A surveillance, epidemiology, and end results survey from 1990 to 2005, J. Thorac. Oncol., 4 (2009), 1524-1529. doi: 10.1097/JTO.0b013e3181ba3634. doi: 10.1097/JTO.0b013e3181ba3634
    [6] K. A. Gold, W. Ii, E. S. Kim, New strategies in squamous cell carcinoma of the lung: Identification of tumor drivers to personalize therapy, Clin. Cancer Res., 18 (2012), 3002-3007. doi: 10.1158/1078-0432.CCR-11-2055. doi: 10.1158/1078-0432.CCR-11-2055
    [7] Y. Kim, C. H. Kim, H. Y. Lee, S. H. Lee, H. S. Kim, S. Lee, et al., Comprehensive clinical and genetic characterization of hyperprogression based on volumetry in advanced non-small cell lung cancer treated with immune checkpoint inhibitor, J. Thorac. Oncol., 14 (2019), 1608-1618. doi: 10.1016/j.jtho.2019.05.033. doi: 10.1016/j.jtho.2019.05.033
    [8] B. Jing, T. Wang, B. Sun, J. Xu, D. Xu, Y. Liao, et al., IL6/STAT3 signaling orchestrates premetastatic niche formation and immunosuppressive traits in lung, Cancer Res., 80 (2020), 784-797. doi: 10.1158/0008-5472.CAN-19-2013. doi: 10.1158/0008-5472.CAN-19-2013
    [9] D. Hanahan, R. A. Weinberg, Hallmarks of cancer: the next generation, Cell, 144 (2011), 646-674. doi: 10.1016/j.cell.2011.02.013. doi: 10.1016/j.cell.2011.02.013
    [10] G. Bindea, B. Mlecnik, M. Tosolini, A. Kirilovsky, M. Waldner, A. C. Obenauf, et al., Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer, Immunity, 39 (2013), 782-795. doi: 10.1016/j.immuni.2013.10.003. doi: 10.1016/j.immuni.2013.10.003
    [11] R. C. Gentleman, V. J. Carey, D. M. Bates, B. Bolstad, M. Dettling, S. Dudoit, et al., Bioconductor: open software development for computational biology and bioinformatics, Genome Biol., 5 (2004), R80. doi: 10.1186/gb-2004-5-10-r80. doi: 10.1186/gb-2004-5-10-r80
    [12] T. R. Bauer, H. E. Mcdermid, M. L. Budarf, M. L. Van Keuren, B. B. Blomberg, Physical location of the human immunoglobulin lambda-like genes, 14.1, 16.1, and 16.2, Immunogenetics, 38 (1993), 387-399. doi: 10.1007/BF00184519. doi: 10.1007/BF00184519
    [13] A. Rody, U. Holtrich, L. Pusztai, C. Liedtke, R. Gaetje, E. Ruckhaeberle, et al., T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers, Breast Cancer Res., 11 (2009), R15. doi: 10.1186/bcr2234. doi: 10.1186/bcr2234
    [14] Q. Liu, R. Cheng, X. Kong, Z. Wang, Y. Fang, J. Wang, Molecular and clinical characterization of PD-1 in breast cancer using large-scale transcriptome data, Front. Immunol., 11 (2020), 558757. doi: 10.3389/fimmu.2020.558757. doi: 10.3389/fimmu.2020.558757
    [15] F. Talab, J. C. Allen, V. Thompson, K. Lin, J. R. Slupsky, LCK is an important mediator of B-cell receptor signaling in chronic lymphocytic leukemia cells, Mol. Cancer Res., 11 (2013), 541-554. doi: 10.1158/1541-7786.MCR-12-0415-t. doi: 10.1158/1541-7786.MCR-12-0415-t
    [16] U. Rother, A. Grussler, C. Griesbach, V. Almasi-Sperling, W. Lang, A. Meyer, Safety of medical compression stockings in patients with diabetes mellitus or peripheral arterial disease, BMJ Open Diabetes Res. Care, 8(2020). doi: 10.1136/bmjdrc-2020-001316. doi: 10.1136/bmjdrc-2020-001316
    [17] T. W. Mudd, C. Lu, J. D. Klement, K. Liu, MS4A1 expression and function in T cells in the colorectal cancer tumor microenvironment, Cell Immunol., 360 (2021), 104260. doi: 10.1016/j.cellimm.2020.104260. doi: 10.1016/j.cellimm.2020.104260
    [18] R. Brigelius-Flohé, P. A. Kipp, Physiological functions of GPx2 and its role in inflammation-triggered carcinogenesis, Ann. N. Y. Acad. Sci., 1259 (2012), 19-25. doi: 10.1111/j.1749-6632.2012.06574.x. doi: 10.1111/j.1749-6632.2012.06574.x
  • Reader Comments
  • © 2022 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(2894) PDF downloads(116) Cited by(1)

Article outline

Figures and Tables

Figures(8)  /  Tables(5)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog