Prognostic Risk of Immune-associated Signature in the Microenvironment of Brain Gliomas

Overview

Journal Front Genet

Date 2023 Oct 23

PMID 37867596

Authors

Yaling Tao

Junqi Zhu

Xiaoling Yu

Huaiwei Cong

Jinpeng Li

Ting Cai

Qian Chen

Affiliations

Soon will be listed here.

Abstract

Understanding the key factors in the tumor microenvironment (TME) that affect the prognosis of gliomas is crucial. In this study, we sought to uncover the prognostic significance of immune cells and immune-related genes in the TME of gliomas. We incorporated data of 970 glioma patient samples from the Chinese Glioma Genome Atlas (CGGA) database as the training set, and an additional set of 666 samples from The Cancer Genome Atlas (TCGA) database served as the validation set. From our analysis, we identified 21 immune-related differentially expressed genes (DEGs) in the TME, which holds implications for glioma prognosis. Based on these genes, we constructed a prognostic risk model on the 21 genes. The prognostic risk model demonstrated robust performance with an area under the curve (AUC) value of 0.848. Notably, the risk score derived from the model emerged as an independent prognostic factor of gliomas, with high risk scores indicative of an unfavorable prognosis. Furthermore, we observed that high infiltration levels of certain immune cells, namely, activated dendritic cells, M0 macrophages, M2 macrophages, and regulatory T cells (Tregs), correlated with an unfavorable glioma prognosis. In conclusion, our findings suggested that the TME of gliomas harbored a distinct immune-associated signature, comprising 21 immune-related genes and specific immune cells. These elements significantly influence the prognosis and present potential as novel indicators in the clinical assessment of glioma patient outcomes.

References

Thomas D, Massague J . TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell. 2005; 8(5):369-80. DOI: 10.1016/j.ccr.2005.10.012. View

Khasraw M, Ameratunga M, Grant R, Wheeler H, Pavlakis N . Antiangiogenic therapy for high-grade glioma. Cochrane Database Syst Rev. 2014; (9):CD008218. DOI: 10.1002/14651858.CD008218.pub3. View

Louis D, Ohgaki H, Wiestler O, Cavenee W, Burger P, Jouvet A . The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007; 114(2):97-109. PMC: 1929165. DOI: 10.1007/s00401-007-0243-4. View

Liu Y, Chen X, Cheng R, Yang F, Yu M, Wang C . The Jun/miR-22/HuR regulatory axis contributes to tumourigenesis in colorectal cancer. Mol Cancer. 2018; 17(1):11. PMC: 5775639. DOI: 10.1186/s12943-017-0751-3. View

Furnari F, Fenton T, Bachoo R, Mukasa A, Stommel J, Stegh A . Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007; 21(21):2683-710. DOI: 10.1101/gad.1596707. View

Reuss D, Mamatjan Y, Schrimpf D, Capper D, Hovestadt V, Kratz A . IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. Acta Neuropathol. 2015; 129(6):867-73. PMC: 4500039. DOI: 10.1007/s00401-015-1438-8. View

Fakih M, Ouyang C, Wang C, Tu T, Gozo M, Cho M . Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome. J Clin Invest. 2019; 129(10):4464-4476. PMC: 6763253. DOI: 10.1172/JCI127046. View

Zeng D, Li M, Zhou R, Zhang J, Sun H, Shi M . Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures. Cancer Immunol Res. 2019; 7(5):737-750. DOI: 10.1158/2326-6066.CIR-18-0436. View

Yang S, Liu T, Nan H, Wang Y, Chen H, Zhang X . Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of cutaneous melanoma. J Cell Physiol. 2019; 235(2):1025-1035. DOI: 10.1002/jcp.29018. View

10.

Speiser D, Ho P, Verdeil G . Regulatory circuits of T cell function in cancer. Nat Rev Immunol. 2016; 16(10):599-611. DOI: 10.1038/nri.2016.80. View

11.

Schmieder A, Michel J, Schonhaar K, Goerdt S, Schledzewski K . Differentiation and gene expression profile of tumor-associated macrophages. Semin Cancer Biol. 2012; 22(4):289-97. DOI: 10.1016/j.semcancer.2012.02.002. View

12.

Brown C, Starr R, Aguilar B, Shami A, Martinez C, DApuzzo M . Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells. Clin Cancer Res. 2012; 18(8):2199-209. PMC: 3578382. DOI: 10.1158/1078-0432.CCR-11-1669. View

13.

Bao M, Lv Q, Szeto V, Wong R, Zhu S, Zhang Y . TRPM2-AS inhibits the growth, migration, and invasion of gliomas through JNK, c-Jun, and RGS4. J Cell Physiol. 2019; 235(5):4594-4604. DOI: 10.1002/jcp.29336. View

14.

Tan Y, Li Y, Yan T, Xu Y, Liu B, Yang J . Six Immune Associated Genes Construct Prognostic Model Evaluate Low-Grade Glioma. Front Immunol. 2021; 11:606164. PMC: 7779629. DOI: 10.3389/fimmu.2020.606164. View

15.

Brown C, Alizadeh D, Starr R, Weng L, Wagner J, Naranjo A . Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med. 2016; 375(26):2561-9. PMC: 5390684. DOI: 10.1056/NEJMoa1610497. View

16.

Pages F, Mlecnik B, Marliot F, Bindea G, Ou F, Bifulco C . International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018; 391(10135):2128-2139. DOI: 10.1016/S0140-6736(18)30789-X. View

17.

Tan A, Ashley D, Lopez G, Malinzak M, Friedman H, Khasraw M . Management of glioblastoma: State of the art and future directions. CA Cancer J Clin. 2020; 70(4):299-312. DOI: 10.3322/caac.21613. View

18.

Iyengar N, Gucalp A, Dannenberg A, Hudis C . Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation. J Clin Oncol. 2016; 34(35):4270-4276. PMC: 5562428. DOI: 10.1200/JCO.2016.67.4283. View

19.

Kawakami M, Kawakami K, Takahashi S, Abe M, Puri R . Analysis of interleukin-13 receptor alpha2 expression in human pediatric brain tumors. Cancer. 2004; 101(5):1036-42. DOI: 10.1002/cncr.20470. View

20.

Pignatti F, van den Bent M, Curran D, Debruyne C, Sylvester R, Therasse P . Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol. 2002; 20(8):2076-84. DOI: 10.1200/JCO.2002.08.121. View