Identification of the novel prognostic biomarker, MLLT11, reveals its relationship with immune checkpoint markers in glioma

Abstract

AimThis study aimed to explore the expression pattern of MLLT11 under different pathological features, evaluate its prognostic value for glioma patients, reveal the relationship between MLLT11 mRNA expression and immune cell infiltration in the tumor microenvironment (TME), and provide more evidence for the molecular diagnosis of glioma and immunotherapy.MethodsUsing large-scale bioinformatic approach and RNA sequencing (RNA-seq) data from public databases The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and The Gene Expression Omnibus (GEO)), we investigated the relationship between MLLT11 mRNA levels and pathologic characteristics. The distribution in the different subtypes was observed based on Verhaak bulk and Neftel single-cell classification. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used for bioinformatic analysis. Kaplan–Meier survival analysis and Cox regression analysis were used for survival analysis. Correlation analyses were performed between MLLT11 expression and 22 immune cells and immune checkpoints in the TME.ResultsWe found that MLLT11 expression is decreased in high-grade glioma tissues; we further verified this result by RT­PCR, Western blotting, and immunohistochemistry using our clinical samples. According to the Verhaak classification, high MLLT11 expression is mostly clustered in pro-neutral (PN) and neutral (NE) subtypes, while in the Neftel classification, MLLT11 mainly clustered in neural progenitor-like (NPC-like) neoplastic cells. Survival analysis revealed that low levels of MLLT11 expression are associated with a poorer prognosis; MLLT11 was identified as an independent prognostic factor in multivariate Cox regression analyses. Functional enrichment analyses of MLLT11 with correlated expression indicated that low MLLT11 expression is associated with the biological process related to the extracellular matrix, and the high expression group is related to the synaptic structure. Correlation analyses suggest that declined MLLT11 expression is associated with increased macrophage infiltration in glioma, especially M2 macrophage, and verified by RT­PCR, Western blotting, and immunohistochemistry using our clinical glioma samples. MLLT11 had a highly negative correlation with immune checkpoint inhibitor (ICI) genes including PDCD1, PD-L1, TIM3(HAVCR2), and PD‐L2 (PDCD1LG2).ConclusionMLLT11 plays a crucial role in the progression of glioma and has the potential to be a new prognostic marker for glioma.

Integrative Analysis of the Predictive Value of Perilipin Family on Clinical Significance, Prognosis and Immunotherapy of Glioma

“…In addition, IDH mutation status and 1p/19q co-deletion status have been considered as crucial indicators for the malignant classification and prognosis prediction of glioma [ 46 ]. Most glioma patients with IDH mutation and 1p19q co-deletion status have a relatively favorable prognosis, which is a vital indicator for stratification in clinical trials [ 47 ]. Expression levels of PLINs were analyzed in 1p19q non-codel and IDH wild-type subtypes, and PLIN2/3 expression was found to be increased in 1p19q non-codel and IDH wild-type subtypes.…”

MLLT11 Regulates Endometrial Stroma Cell Adhesion, Proliferation and Survival in Ectopic Lesions of Women with Advanced Endometriosis

“…MLLT11 is a gene implicated in hematopoietic progenitor cell differentiation [ 31 ] and neuronal cell differentiation [ 32 ]. In a pathogenic context, MLLT11 has been reported to play an oncogenic role in the development and progression of a variety of human cancers [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ] and to act as a tumor suppressor in glioma neural carcinomas [ 21 ]. However, the role for MLLT11 in the pathogenesis of endometriosis has not been previously reported.…”

“…A functional role of MLLT11 in tumor progression was also reported in human breast [ 17 ] and endometrial carcinomas [ 18 ], as well as in a number of other human solid tumors [ 19 , 20 ]. In contrast to this oncogenic role, in the nervous system, MLLT11 functions as a tumor suppressor, with a high level of expression in normal brain tissues compared with decreased expression correlating with the malignant tumor grade [ 21 ].…”