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The Diagnostic and Prognostic Value of the Immune Checkpoint BGN in Thymoma

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Abstract

Thymoma is frequently correlated with various autoimmune diseases. However, unequivocal therapeutic targets for thymoma remain undefined, and the role of immune checkpoints in the development of thymoma-related autoimmune illnesses is unclear. We examined 39 thymoma samples and 44 normal control samples from the GEO database. Following batch correction, we identified 224 Differentially Expressed Genes (DEGs) using the Limma package. We employed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to enrich for functional pathways of DEGs. We utilized a Protein–Protein Interaction (PPI) network to identify hub genes and determine their correlation with immune cell infiltration using CIBERSORT. Real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical staining were implemented to verify identified hub genes in vivo. Simultaneously, we evaluated the prognostic relevance of the hub gene using clinical data. We determined COL1A1, COL1A2, and BGN to be the central hub genes in thymoma. Validation via RT-qPCR, Western blot, and immunohistochemical staining established significant statistical divergence between thymoma tissue and the normal thymus for only BGN. Expression levels of BGN showed strong negative correlation with the infiltration level of B cells and CD4+ T cells, yet a significant positive correlation with the level of neutrophil infiltration. We found high immune infiltration levels of macrophages, NK cells, and Th1 cells in the thymoma microenvironment in patients with a high expression of BGN. Co-localization of BGN and macrophages within thymoma tissue was discerned via tissue staining. Clinical data dictated that thymoma patients exhibiting elevated BGN expression underwent longer hospital stays, longer lengths in intensive care units, greater hospitalization costs, and extended ventilator usage; our study, augmented by clinical information, recognized BGN as possessive of diagnostic and prognostic significance in thymoma through in silico and molecular verification experiments. Our findings offered an important objective for thymoma-treated autoimmune disease comprehension, supplemented by the strong association with immune infiltration.

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Data Availability

All data can be obtained from TCGA and GEO cohorts.

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Acknowledgements

We gratefully thank the contributions from the websites of TCGA, GEO, TRRUST, and TIMER.

Funding

This research was funded by the Beijing-Tianjin-Hebei Basic Research Cooperation Project, 19JCZDJC64400; the Tianjin Northern Medicine Development Foundation, TJNMDF2020YB-01; the Tianjin Northern Medicine Development Foundation, TJNMDF2020ZD-01; the Tianjin Natural Science Foundation of Key Program, 19JCZDJC35500; and the Tianjin Natural Science Foundation of Youth Program, 19JCQNJC12000.

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Author notes

  1. Yuxin Liu, Si Chen, and Yan Wang have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Cardiovascular Thoracic Surgery, Tianjin Medical University General Hospital, Anshan Road No. 154, Heping District, Tianjin, 300052, China

    Yuxin Liu, Si Chen, Yan Wang, Zeyang Zhang, Jianyao Wang & Peng Zhang

  2. School of Clinical Medicine, Tsinghua University, Beijing, China

    Ziyi Wang

  3. Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, China

    Ziyou Tao

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  1. Yuxin Liu
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  2. Si Chen
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Contributions

Conceptualization, PZ and YL; methodology, YL and SC and YW; formal analysis, ZZ and JW; investigation, YW and ZT; data curation, YL and ZW; writing and preparation of the original draft, YL, SC, and YW; writing, reviewing, and editing of the manuscript, PZ and YL; visualization, YL; supervision, PZ; project administration, PZ; and funding acquisition, PZ All authors have read and agreed to the published version of the manuscript.

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Correspondence to Peng Zhang.

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Liu, Y., Chen, S., Wang, Y. et al. The Diagnostic and Prognostic Value of the Immune Checkpoint BGN in Thymoma. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10523-5

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