Pathway analysis of CD8+ T cell transcriptome in glioblastoma patients reveales multiple sclerosis signaling pathway as the top rated upregulated disease pathway in tumor infiltrating cells
Аутори
Stefanović, MilanJovanović, Ivan
Stanković, Aleksandra
Živković, Maja
Остала ауторства
Morić, IvanaĐorđević, Valentina
Конференцијски прилог (Објављена верзија)
,
© 2023 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт
The significance of CD8+ T cell central nervous system migration and activation in the
progression of glioblastoma is well documented. However, molecular signaling pathways
regulation related to migration and activation in CD8+ cells in glioblastoma is scarce.
Therefore we have analyzed the molecular pathway regulation in differentially expressed
mRNAs of tumor infiltrating vs. peripheral blood CD8+ T cells from glioblastoma patients.
Tumor-infiltrating vs. peripheral blood differentially expressed mRNAs were obtained
by analyzing the FASTAQ files on the Galaxy platform using the LimmaVoom tool with
filtering low count mRNAs (CPM > 2). We used publically avaliable FASTAQ files with CD8+
T cells mRNA sequencing data deposited at NCBI’s GEO database (accession number
GSE171197). The differentially expressed mRNA were analyzed with Qiagen’s Ingenuity
pathway analysis (p adj. cutoff 0.05). Protein-protein interaction network was constructed
on the NetworkAnalyst platform using t...he IMeX database with minimal order parameters.
The top rated disease canonical pathway was the multiple sclerosis (MS) signaling
pathway, with 18 differentially expressed mRNA hits (out of possible 222), p adj. = 0.0009
and Z score = 2.828, implying significant upregulation of this pathway in tumor-infiltrating
CD8+ T cells.
The MS signaling pathway describes the molecular cascade which leads to the autoimmune
phenotype in lymphocytes, including activation and central nervous tissue infiltration. To
further specify the aspects of the canonical MS signaling pathway which might influence
tumor infiltrating phenotype we have constructed a minimal order protein-protein
interaction network. Results showed a number of lymphocyte migration and activation
KEGG terms within the network, such as: TNF signaling pathway (p adj. = 0.0000115),
IL-17 signaling pathway (p adj. = 0.00000427), sphingolipid signaling pathway (p adj. =
0.00171), NF-kappa B signaling pathway (p adj. = 0.0000694) and TCR signaling pathway
(p adj. = 0.0071).
We conclude that MS signaling pathway is an viable model for further understanding of
the transcriptional phenotype of glioblastoma infiltrating CD8+ T killer cells, illustrating
that same migration and activation mechanisms which mediate brain autoimmunity are
essential for brain antitumor adaptive immunity.
Кључне речи:
glioblastoma / multiple sclerosis / enrichment analysis / network analysisИзвор:
4th Belgrade Bioinformatics Conference, 2023, 4, 104-104Издавач:
- Belgrade : Institute of molecular genetics and genetic engineering
Напомена:
- Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 2023
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Stefanović, Milan AU - Jovanović, Ivan AU - Stanković, Aleksandra AU - Živković, Maja PY - 2023 UR - 978-86-82679-14-1 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2049 AB - The significance of CD8+ T cell central nervous system migration and activation in the progression of glioblastoma is well documented. However, molecular signaling pathways regulation related to migration and activation in CD8+ cells in glioblastoma is scarce. Therefore we have analyzed the molecular pathway regulation in differentially expressed mRNAs of tumor infiltrating vs. peripheral blood CD8+ T cells from glioblastoma patients. Tumor-infiltrating vs. peripheral blood differentially expressed mRNAs were obtained by analyzing the FASTAQ files on the Galaxy platform using the LimmaVoom tool with filtering low count mRNAs (CPM > 2). We used publically avaliable FASTAQ files with CD8+ T cells mRNA sequencing data deposited at NCBI’s GEO database (accession number GSE171197). The differentially expressed mRNA were analyzed with Qiagen’s Ingenuity pathway analysis (p adj. cutoff 0.05). Protein-protein interaction network was constructed on the NetworkAnalyst platform using the IMeX database with minimal order parameters. The top rated disease canonical pathway was the multiple sclerosis (MS) signaling pathway, with 18 differentially expressed mRNA hits (out of possible 222), p adj. = 0.0009 and Z score = 2.828, implying significant upregulation of this pathway in tumor-infiltrating CD8+ T cells. The MS signaling pathway describes the molecular cascade which leads to the autoimmune phenotype in lymphocytes, including activation and central nervous tissue infiltration. To further specify the aspects of the canonical MS signaling pathway which might influence tumor infiltrating phenotype we have constructed a minimal order protein-protein interaction network. Results showed a number of lymphocyte migration and activation KEGG terms within the network, such as: TNF signaling pathway (p adj. = 0.0000115), IL-17 signaling pathway (p adj. = 0.00000427), sphingolipid signaling pathway (p adj. = 0.00171), NF-kappa B signaling pathway (p adj. = 0.0000694) and TCR signaling pathway (p adj. = 0.0071). We conclude that MS signaling pathway is an viable model for further understanding of the transcriptional phenotype of glioblastoma infiltrating CD8+ T killer cells, illustrating that same migration and activation mechanisms which mediate brain autoimmunity are essential for brain antitumor adaptive immunity. PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 4th Belgrade Bioinformatics Conference T1 - Pathway analysis of CD8+ T cell transcriptome in glioblastoma patients reveales multiple sclerosis signaling pathway as the top rated upregulated disease pathway in tumor infiltrating cells EP - 104 SP - 104 VL - 4 UR - https://hdl.handle.net/21.15107/rcub_imagine_2049 ER -
@conference{ author = "Stefanović, Milan and Jovanović, Ivan and Stanković, Aleksandra and Živković, Maja", year = "2023", abstract = "The significance of CD8+ T cell central nervous system migration and activation in the progression of glioblastoma is well documented. However, molecular signaling pathways regulation related to migration and activation in CD8+ cells in glioblastoma is scarce. Therefore we have analyzed the molecular pathway regulation in differentially expressed mRNAs of tumor infiltrating vs. peripheral blood CD8+ T cells from glioblastoma patients. Tumor-infiltrating vs. peripheral blood differentially expressed mRNAs were obtained by analyzing the FASTAQ files on the Galaxy platform using the LimmaVoom tool with filtering low count mRNAs (CPM > 2). We used publically avaliable FASTAQ files with CD8+ T cells mRNA sequencing data deposited at NCBI’s GEO database (accession number GSE171197). The differentially expressed mRNA were analyzed with Qiagen’s Ingenuity pathway analysis (p adj. cutoff 0.05). Protein-protein interaction network was constructed on the NetworkAnalyst platform using the IMeX database with minimal order parameters. The top rated disease canonical pathway was the multiple sclerosis (MS) signaling pathway, with 18 differentially expressed mRNA hits (out of possible 222), p adj. = 0.0009 and Z score = 2.828, implying significant upregulation of this pathway in tumor-infiltrating CD8+ T cells. The MS signaling pathway describes the molecular cascade which leads to the autoimmune phenotype in lymphocytes, including activation and central nervous tissue infiltration. To further specify the aspects of the canonical MS signaling pathway which might influence tumor infiltrating phenotype we have constructed a minimal order protein-protein interaction network. Results showed a number of lymphocyte migration and activation KEGG terms within the network, such as: TNF signaling pathway (p adj. = 0.0000115), IL-17 signaling pathway (p adj. = 0.00000427), sphingolipid signaling pathway (p adj. = 0.00171), NF-kappa B signaling pathway (p adj. = 0.0000694) and TCR signaling pathway (p adj. = 0.0071). We conclude that MS signaling pathway is an viable model for further understanding of the transcriptional phenotype of glioblastoma infiltrating CD8+ T killer cells, illustrating that same migration and activation mechanisms which mediate brain autoimmunity are essential for brain antitumor adaptive immunity.", publisher = "Belgrade : Institute of molecular genetics and genetic engineering", journal = "4th Belgrade Bioinformatics Conference", title = "Pathway analysis of CD8+ T cell transcriptome in glioblastoma patients reveales multiple sclerosis signaling pathway as the top rated upregulated disease pathway in tumor infiltrating cells", pages = "104-104", volume = "4", url = "https://hdl.handle.net/21.15107/rcub_imagine_2049" }
Stefanović, M., Jovanović, I., Stanković, A.,& Živković, M.. (2023). Pathway analysis of CD8+ T cell transcriptome in glioblastoma patients reveales multiple sclerosis signaling pathway as the top rated upregulated disease pathway in tumor infiltrating cells. in 4th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 4, 104-104. https://hdl.handle.net/21.15107/rcub_imagine_2049
Stefanović M, Jovanović I, Stanković A, Živković M. Pathway analysis of CD8+ T cell transcriptome in glioblastoma patients reveales multiple sclerosis signaling pathway as the top rated upregulated disease pathway in tumor infiltrating cells. in 4th Belgrade Bioinformatics Conference. 2023;4:104-104. https://hdl.handle.net/21.15107/rcub_imagine_2049 .
Stefanović, Milan, Jovanović, Ivan, Stanković, Aleksandra, Živković, Maja, "Pathway analysis of CD8+ T cell transcriptome in glioblastoma patients reveales multiple sclerosis signaling pathway as the top rated upregulated disease pathway in tumor infiltrating cells" in 4th Belgrade Bioinformatics Conference, 4 (2023):104-104, https://hdl.handle.net/21.15107/rcub_imagine_2049 .