Mutational Profiling of Low-grade Gliomas Identifies Prognosis and Immunotherapy-related Biomarkers and Tumour Immune Microenvironment Characteristics

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2021 Oct 1

PMID 34597473

Citations 14

Authors

Wen-Wen Lin

Guan-Yong Ou

Wei-Jiang Zhao

Affiliations

Soon will be listed here.

Abstract

Low-grade glioma (LGG) is a heterogeneous tumour with the median survival rate less than 10 years. Therefore, it is urgent to develop efficient immunotherapy strategies of LGG. In this study, we analysed mutation profiles based on the data of 510 LGG patients from the Cancer Genome Atlas (TCGA) database and investigated the prognostic value of mutated genes and evaluate their immune infiltration. Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to indicate the characteristics of gliomas that respond to immune checkpoint blockade (ICB) therapy. Univariate and multivariate cox regression analysis was performed to identify indicators to construct the nomogram model. 485 (95.47%) of 508 LGG samples showed gene mutation, and 9 mutated genes were significantly related to overall survival (OS), among which 6 mutated genes were significantly correlated with OS between mutation and wildtypes. Immune infiltration and immune score analyses revealed that these six mutated genes were significantly associated with tumour immune microenvironment in LGG. The response of LGG with different characteristics to ICB was evaluated by TIDE algorithm. Finally, CIC gene was screened through both univariate and multivariate Cox regression analyses, and the nomogram model was established to determine the potential prognostic value of CIC in LGG. Our study provides comprehensive analysis of mutated genes in LGG, supporting modulation of mutated genes in the management of LGG.

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References

Stancheva G, Goranova T, Laleva M, Kamenova M, Mitkova A, Velinov N . IDH1/IDH2 but not TP53 mutations predict prognosis in Bulgarian glioblastoma patients. Biomed Res Int. 2014; 2014:654727. PMC: 4017788. DOI: 10.1155/2014/654727. View

Yin W, Jiang X, Tan J, Xin Z, Zhou Q, Zhan C . Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Model for Lower-Grade Glioma. Front Oncol. 2020; 10:1409. PMC: 7468526. DOI: 10.3389/fonc.2020.01409. View

Sturm D, Pfister S, Jones D . Pediatric Gliomas: Current Concepts on Diagnosis, Biology, and Clinical Management. J Clin Oncol. 2017; 35(21):2370-2377. DOI: 10.1200/JCO.2017.73.0242. View

Liu J, Kang R, Tang D . CDK1/2/5 blockade: killing two birds with one stone. Oncoimmunology. 2021; 10(1):1875612. PMC: 7833763. DOI: 10.1080/2162402X.2021.1875612. View

Li N, Zhang Y, Sidlauskas K, Ellis M, Evans I, Frankel P . Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades. Oncogene. 2018; 37(31):4313-4333. PMC: 6072706. DOI: 10.1038/s41388-018-0277-1. View

Yu S, Zhang Y, Wu Y, Yang H, Chen Y, Yang Y . Subcellular localization of mutated β-catenins with different incidences of -peptide bonds at the Xaa246-P247 site in HepG2 cells. FASEB J. 2019; 33(5):6574-6583. PMC: 6497428. DOI: 10.1096/fj.201801937RR. View

Bodor J, Boumber Y, Borghaei H . Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer. 2019; 126(2):260-270. PMC: 7372560. DOI: 10.1002/cncr.32468. View

Sturm G, Finotello F, List M . Immunedeconv: An R Package for Unified Access to Computational Methods for Estimating Immune Cell Fractions from Bulk RNA-Sequencing Data. Methods Mol Biol. 2020; 2120:223-232. DOI: 10.1007/978-1-0716-0327-7_16. View

Wesseling P, van den Bent M, Perry A . Oligodendroglioma: pathology, molecular mechanisms and markers. Acta Neuropathol. 2015; 129(6):809-27. PMC: 4436696. DOI: 10.1007/s00401-015-1424-1. View

10.

Jiang A, Ren M, Liu N, Gao H, Wang J, Zheng X . Tumor Mutation Burden, Immune Cell Infiltration, and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer. Int J Med Sci. 2021; 18(1):226-238. PMC: 7738958. DOI: 10.7150/ijms.51064. View

11.

Li Z, Yin Y, Liu F . Recent developments in predictive biomarkers of pediatric glioma. Oncol Lett. 2017; 14(1):497-500. PMC: 5494731. DOI: 10.3892/ol.2017.6243. View

12.

Chalakur-Ramireddy N, Pakala S . Combined drug therapeutic strategies for the effective treatment of Triple Negative Breast Cancer. Biosci Rep. 2018; 38(1). PMC: 5789156. DOI: 10.1042/BSR20171357. View

13.

Hui L, Chen Y . Tumor microenvironment: Sanctuary of the devil. Cancer Lett. 2015; 368(1):7-13. DOI: 10.1016/j.canlet.2015.07.039. View

14.

Siegfried G, Descarpentrie J, Evrard S, Khatib A . Proprotein convertases: Key players in inflammation-related malignancies and metastasis. Cancer Lett. 2020; 473:50-61. PMC: 7115805. DOI: 10.1016/j.canlet.2019.12.027. View

15.

Wang Z, Guo X, Gao L, Wang Y, Guo Y, Xing B . Classification of pediatric gliomas based on immunological profiling: implications for immunotherapy strategies. Mol Ther Oncolytics. 2021; 20:34-47. PMC: 7851498. DOI: 10.1016/j.omto.2020.12.012. View

16.

Labussiere M, Sanson M, Idbaih A, Delattre J . IDH1 gene mutations: a new paradigm in glioma prognosis and therapy?. Oncologist. 2010; 15(2):196-9. PMC: 3227941. DOI: 10.1634/theoncologist.2009-0218. View

17.

Rizzo A, Ricci A, Brandi G . PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer. Cancers (Basel). 2021; 13(3). PMC: 7867133. DOI: 10.3390/cancers13030558. View

18.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

19.

Saini M, Jha A, Tangri R, Qudratullah M, Ali S . MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients. Hum Mol Genet. 2020; 29(21):3532-3545. PMC: 7788295. DOI: 10.1093/hmg/ddaa231. View

20.

Fecci P, Sampson J . The current state of immunotherapy for gliomas: an eye toward the future. J Neurosurg. 2019; 131(3):657-666. DOI: 10.3171/2019.5.JNS181762. View