Skip to main content
Top
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Glioblastoma | Research

Prognostic marker CXCL5 in glioblastoma polyformis and its mechanism of immune invasion

Authors: Wangyang Yu, Minfeng Zhou, Huifang Niu, Jinxiao Li, Qiumeng Li, Xiaoyun Xu, Fengxia Liang, Chen Rui

Published in: BMC Cancer | Issue 1/2024

Login to get access

Abstract

Glioblastoma multiforme (GBM) is the most aggressive brain cancer with a poor prognosis. Therefore, the correlative molecular markers and molecular mechanisms should be explored to assess the occurrence and treatment of glioma.WB and qPCR assays were used to detect the expression of CXCL5 in human GBM tissues. The relationship between CXCL5 expression and clinicopathological features was evaluated using logistic regression analysis, Wilcoxon symbolic rank test, and Kruskal–Wallis test. Univariate, multivariate Cox regression and Kaplan–Meier methods were used to assess CXCL5 and other prognostic factors of GBM. Gene set enrichment analysis (GSEA) was used to identify pathways associated with CXCL5. The correlation between CXCL5 and tumor immunoinfiltration was investigated using single sample gene set enrichment analysis (ssGSEA) of TCGA data. Cell experiments and mouse subcutaneous transplanted tumor models were used to evaluate the role of CXCL5 in GBM. WB, qPCR, immunofluorescence, and immunohistochemical assays showed that CXCL5 expression was increased in human GBM tissues. Furthermore, high CXCL5 expression was closely related to poor disease-specific survival and overall survival of GBM patients. The ssGSEA suggested that CXCL5 is closely related to the cell cycle and immune response through PPAR signaling pathway. GSEA also showed that CXCL5 expression was positively correlated with macrophage cell infiltration level and negatively correlated with cytotoxic cell infiltration level. CXCL5 may be associated with the prognosis and immunoinfiltration of GBM.
Appendix
Available only for authorised users
Literature
1.
go back to reference Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, Nishikawa R, Rosenthal M, Wen PY, Stupp R, Reifenberger G. Glioma. Nat Rev Dis Primers. 2015;1:15017.CrossRefPubMed Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, Nishikawa R, Rosenthal M, Wen PY, Stupp R, Reifenberger G. Glioma. Nat Rev Dis Primers. 2015;1:15017.CrossRefPubMed
2.
go back to reference Cao F, Fan Y, Yu Y, Yang G, Zhong H. Dissecting prognosis modules and biomarkers in glioblastoma based on weighted gene co-expression network analysis. Cancer Manag Res. 2021;13:5477–89.CrossRefPubMedPubMedCentral Cao F, Fan Y, Yu Y, Yang G, Zhong H. Dissecting prognosis modules and biomarkers in glioblastoma based on weighted gene co-expression network analysis. Cancer Manag Res. 2021;13:5477–89.CrossRefPubMedPubMedCentral
3.
go back to reference Drongitis D, Verrillo L, De Marinis P, Orabona P, Caiola A, Turitto G, Alfieri A, Bruscella S, Gentile M, Moriello V, Sannino E, Di Muccio I, Costa V, Miano MG, de Bellis A. The chromatin-oxygen sensor gene KDM5C associates with novel hypoxia-related signatures in glioblastoma multiforme. Int J Mol Sci. 2022;23(18):10250.CrossRefPubMedPubMedCentral Drongitis D, Verrillo L, De Marinis P, Orabona P, Caiola A, Turitto G, Alfieri A, Bruscella S, Gentile M, Moriello V, Sannino E, Di Muccio I, Costa V, Miano MG, de Bellis A. The chromatin-oxygen sensor gene KDM5C associates with novel hypoxia-related signatures in glioblastoma multiforme. Int J Mol Sci. 2022;23(18):10250.CrossRefPubMedPubMedCentral
4.
go back to reference Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709–22.CrossRefPubMed Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709–22.CrossRefPubMed
5.
go back to reference Jiang N, Xie B, Xiao W, Fan M, Xu S, Duan Y, Hamsafar Y, Evans AC, Huang J, Zhou W, Lin X, Ye N, Wanggou S, Chen W, Jing D, Fragoso RC, Dugger BN, Wilson PF, Coleman MA, Xia S, Li X, Sun LQ, Monjazeb AM, Wang A, Murphy WJ, Kung HJ, Lam KS, Chen HW, Li JJ. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion. Nat Commun. 2022;13(1):1511.CrossRefPubMedPubMedCentral Jiang N, Xie B, Xiao W, Fan M, Xu S, Duan Y, Hamsafar Y, Evans AC, Huang J, Zhou W, Lin X, Ye N, Wanggou S, Chen W, Jing D, Fragoso RC, Dugger BN, Wilson PF, Coleman MA, Xia S, Li X, Sun LQ, Monjazeb AM, Wang A, Murphy WJ, Kung HJ, Lam KS, Chen HW, Li JJ. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion. Nat Commun. 2022;13(1):1511.CrossRefPubMedPubMedCentral
6.
go back to reference Uddin MS, Mamun AA, Alghamdi BS, Tewari D, Jeandet P, Sarwar MS, Ashraf GM. Epigenetics of glioblastoma multiforme: from molecular mechanisms to therapeutic approaches. Semin Cancer Biol. 2022;83:100–20.CrossRefPubMed Uddin MS, Mamun AA, Alghamdi BS, Tewari D, Jeandet P, Sarwar MS, Ashraf GM. Epigenetics of glioblastoma multiforme: from molecular mechanisms to therapeutic approaches. Semin Cancer Biol. 2022;83:100–20.CrossRefPubMed
7.
go back to reference Karsy M, Guan J, Cohen AL, Jensen RL, Colman H. New molecular considerations for glioma: IDH, ATRX, BRAF, TERT, H3 K27M. Curr Neurol Neurosci Rep. 2017;17(2):19.CrossRefPubMed Karsy M, Guan J, Cohen AL, Jensen RL, Colman H. New molecular considerations for glioma: IDH, ATRX, BRAF, TERT, H3 K27M. Curr Neurol Neurosci Rep. 2017;17(2):19.CrossRefPubMed
8.
go back to reference Eskilsson E, Rosland GV, Solecki G, Wang Q, Harter PN, Graziani G, Verhaak RGW, Winkler F, Bjerkvig R, Miletic H. EGFR heterogeneity and implications for therapeutic intervention in glioblastoma. Neuro Oncol. 2018;20(6):743–52.CrossRefPubMed Eskilsson E, Rosland GV, Solecki G, Wang Q, Harter PN, Graziani G, Verhaak RGW, Winkler F, Bjerkvig R, Miletic H. EGFR heterogeneity and implications for therapeutic intervention in glioblastoma. Neuro Oncol. 2018;20(6):743–52.CrossRefPubMed
9.
go back to reference Syafruddin SE, Nazarie W, Moidu NA, Soon BH, Mohtar MA. Integration of RNA-Seq and proteomics data identifies glioblastoma multiforme surfaceome signature. BMC Cancer. 2021;21(1):850.CrossRefPubMedPubMedCentral Syafruddin SE, Nazarie W, Moidu NA, Soon BH, Mohtar MA. Integration of RNA-Seq and proteomics data identifies glioblastoma multiforme surfaceome signature. BMC Cancer. 2021;21(1):850.CrossRefPubMedPubMedCentral
10.
12.
go back to reference Roesch S, Rapp C, Dettling S, Herold-Mende C. When immune cells turn bad-tumor-associated microglia/macrophages in glioma. Int J Mol Sci. 2018;19(2):436.CrossRefPubMedPubMedCentral Roesch S, Rapp C, Dettling S, Herold-Mende C. When immune cells turn bad-tumor-associated microglia/macrophages in glioma. Int J Mol Sci. 2018;19(2):436.CrossRefPubMedPubMedCentral
13.
go back to reference Kim Y, Lee D, Lawler S. Collective invasion of glioma cells through OCT1 signalling and interaction with reactive astrocytes after surgery. Philos Trans R Soc Lond B Biol Sci. 1807;2020(375):20190390. Kim Y, Lee D, Lawler S. Collective invasion of glioma cells through OCT1 signalling and interaction with reactive astrocytes after surgery. Philos Trans R Soc Lond B Biol Sci. 1807;2020(375):20190390.
14.
go back to reference Rutledge WC, Kong J, Gao J, Gutman DA, Cooper LA, Appin C, Park Y, Scarpace L, Mikkelsen T, Cohen ML, Aldape KD, McLendon RE, Lehman NL, Miller CR, Schniederjan MJ, Brennan CW, Saltz JH, Moreno CS, Brat DJ. Tumor-infiltrating lymphocytes in glioblastoma are associated with specific genomic alterations and related to transcriptional class. Clin Cancer Res. 2013;19(18):4951–60.CrossRefPubMed Rutledge WC, Kong J, Gao J, Gutman DA, Cooper LA, Appin C, Park Y, Scarpace L, Mikkelsen T, Cohen ML, Aldape KD, McLendon RE, Lehman NL, Miller CR, Schniederjan MJ, Brennan CW, Saltz JH, Moreno CS, Brat DJ. Tumor-infiltrating lymphocytes in glioblastoma are associated with specific genomic alterations and related to transcriptional class. Clin Cancer Res. 2013;19(18):4951–60.CrossRefPubMed
15.
go back to reference Feng P, Li Z, Li Y, Zhang Y, Miao X. Characterization of different subtypes of immune cell infiltration in glioblastoma to aid immunotherapy. Front Immunol. 2022;13:799509.CrossRefPubMedPubMedCentral Feng P, Li Z, Li Y, Zhang Y, Miao X. Characterization of different subtypes of immune cell infiltration in glioblastoma to aid immunotherapy. Front Immunol. 2022;13:799509.CrossRefPubMedPubMedCentral
17.
go back to reference Zhao J, Ou B, Han D, Wang P, Zong Y, Zhu C, Liu D, Zheng M, Sun J, Feng H, Lu A. Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3beta/beta-catenin pathways. Mol Cancer. 2017;16(1):70.CrossRefPubMedPubMedCentral Zhao J, Ou B, Han D, Wang P, Zong Y, Zhu C, Liu D, Zheng M, Sun J, Feng H, Lu A. Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3beta/beta-catenin pathways. Mol Cancer. 2017;16(1):70.CrossRefPubMedPubMedCentral
18.
go back to reference Yu PF, Huang Y, Han YY, Lin LY, Sun WH, Rabson AB, Wang Y, Shi YF. TNFalpha-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2(+) neutrophils. Oncogene. 2017;36(4):482–90.CrossRefPubMed Yu PF, Huang Y, Han YY, Lin LY, Sun WH, Rabson AB, Wang Y, Shi YF. TNFalpha-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2(+) neutrophils. Oncogene. 2017;36(4):482–90.CrossRefPubMed
19.
go back to reference Umansky V, Blattner C, Fleming V, Hu X, Gebhardt C, Altevogt P, Utikal J. Myeloid-derived suppressor cells and tumor escape from immune surveillance. Semin Immunopathol. 2017;39(3):295–305.CrossRefPubMed Umansky V, Blattner C, Fleming V, Hu X, Gebhardt C, Altevogt P, Utikal J. Myeloid-derived suppressor cells and tumor escape from immune surveillance. Semin Immunopathol. 2017;39(3):295–305.CrossRefPubMed
20.
go back to reference Wu W, Klockow JL, Zhang M, Lafortune F, Chang E, Jin L, Wu Y, Daldrup-Link HE. Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance. Pharmacol Res. 2021;171:105780.CrossRefPubMedPubMedCentral Wu W, Klockow JL, Zhang M, Lafortune F, Chang E, Jin L, Wu Y, Daldrup-Link HE. Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance. Pharmacol Res. 2021;171:105780.CrossRefPubMedPubMedCentral
21.
go back to reference Wang J, Toregrosa-Allen S, Elzey BD, Utturkar S, Lanman NA, Bernal-Crespo V, Behymer MM, Knipp GT, Yun Y, Veronesi MC, Sinn AL, Pollok KE, Brutkiewicz RR, Nevel KS, Matosevic S. Multispecific targeting of glioblastoma with tumor microenvironment-responsive multifunctional engineered NK cells. Proc Natl Acad Sci U S A. 2021;118(45):e2107507118.CrossRefPubMedPubMedCentral Wang J, Toregrosa-Allen S, Elzey BD, Utturkar S, Lanman NA, Bernal-Crespo V, Behymer MM, Knipp GT, Yun Y, Veronesi MC, Sinn AL, Pollok KE, Brutkiewicz RR, Nevel KS, Matosevic S. Multispecific targeting of glioblastoma with tumor microenvironment-responsive multifunctional engineered NK cells. Proc Natl Acad Sci U S A. 2021;118(45):e2107507118.CrossRefPubMedPubMedCentral
22.
go back to reference Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro Oncol. 2020;22(12 Suppl 2):iv1–96. Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro Oncol. 2020;22(12 Suppl 2):iv1–96.
23.
go back to reference Doucette T, Rao G, Rao A, Shen L, Aldape K, Wei J, Dziurzynski K, Gilbert M, Heimberger AB. Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas. Cancer Immunol Res. 2013;1(2):112–22.CrossRefPubMed Doucette T, Rao G, Rao A, Shen L, Aldape K, Wei J, Dziurzynski K, Gilbert M, Heimberger AB. Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas. Cancer Immunol Res. 2013;1(2):112–22.CrossRefPubMed
24.
go back to reference Mahmoud AB, Ajina R, Aref S, Darwish M, Alsayb M, Taher M, AlSharif SA, Hashem AM, Alkayyal AA. Advances in immunotherapy for glioblastoma multiforme. Front Immunol. 2022;13:944452.CrossRefPubMedPubMedCentral Mahmoud AB, Ajina R, Aref S, Darwish M, Alsayb M, Taher M, AlSharif SA, Hashem AM, Alkayyal AA. Advances in immunotherapy for glioblastoma multiforme. Front Immunol. 2022;13:944452.CrossRefPubMedPubMedCentral
26.
go back to reference Joseph JV, Magaut CRS, Storevik LH, Geraldo T, Mathivet MA, Latif J, Rudewicz J, Guyon M, Gambaretti F, Haukas A, Trones LA, RomoYstaas JA, Hossain S, Ninzima S, Cuvellier W, Zhou T, Tomar B, Klink L, Rane BK, Irving J, Marrison P, O’Toole H, Wurdak J, Wang Z, Di E, Birkeland FS, Berven F, Winkler FAE, Kruyt A, Bikfalvi R, Bjerkvig T, Daubon H. Miletic, TGF-beta promotes microtube formation in glioblastoma through thrombospondin 1. Neuro Oncol. 2022;24(4):541–53.CrossRefPubMed Joseph JV, Magaut CRS, Storevik LH, Geraldo T, Mathivet MA, Latif J, Rudewicz J, Guyon M, Gambaretti F, Haukas A, Trones LA, RomoYstaas JA, Hossain S, Ninzima S, Cuvellier W, Zhou T, Tomar B, Klink L, Rane BK, Irving J, Marrison P, O’Toole H, Wurdak J, Wang Z, Di E, Birkeland FS, Berven F, Winkler FAE, Kruyt A, Bikfalvi R, Bjerkvig T, Daubon H. Miletic, TGF-beta promotes microtube formation in glioblastoma through thrombospondin 1. Neuro Oncol. 2022;24(4):541–53.CrossRefPubMed
27.
go back to reference Abdelfattah NP, Kumar C, Wang JS, Leu WF, Flynn R, Gao DS, Baskin K, Pichumani OB, Ijare SL, Wood SZ, Powell DL, Haviland BC, Parker Kerrigan FF, Lang SS, Prabhu KM, Huntoon W, Jiang BYS, Kim J, George K. Yun, Single-cell analysis of human glioma and immune cells as an immunotherapy target. Nat Commun. 2022;13(1):767.CrossRefPubMedPubMedCentral Abdelfattah NP, Kumar C, Wang JS, Leu WF, Flynn R, Gao DS, Baskin K, Pichumani OB, Ijare SL, Wood SZ, Powell DL, Haviland BC, Parker Kerrigan FF, Lang SS, Prabhu KM, Huntoon W, Jiang BYS, Kim J, George K. Yun, Single-cell analysis of human glioma and immune cells as an immunotherapy target. Nat Commun. 2022;13(1):767.CrossRefPubMedPubMedCentral
Metadata
Title
Prognostic marker CXCL5 in glioblastoma polyformis and its mechanism of immune invasion
Authors
Wangyang Yu
Minfeng Zhou
Huifang Niu
Jinxiao Li
Qiumeng Li
Xiaoyun Xu
Fengxia Liang
Chen Rui
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11650-3

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine