Profiling pro-neural to mesenchymal transition identifies a lncRNA signature in glioma

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Journal of Translational Medicine Open Access

RESEARCH

Profiling pro‑neural to mesenchymal transition identifies a lncRNA signature in glioma Qingyu Liang1, Gefei Guan1, Xue Li1, Chunmi Wei2, Jianqi Wu1, Peng Cheng1, Anhua Wu1* and Wen Cheng1* 

Abstract  Background:  Molecular classification has laid the framework for exploring glioma biology and treatment strategies. Pro-neural to mesenchymal transition (PMT) of glioma is known to be associated with aggressive phenotypes, unfavorable prognosis, and treatment resistance. Recent studies have highlighted that long non-coding RNAs (lncRNAs) are key mediators in cancer mesenchymal transition. However, the relationship between lncRNAs and PMT in glioma has not been systematically investigated. Methods:  Gene expression profiles from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GSE16011, and Rembrandt with available clinical and genomic information were used for analyses. Bioinformatics methods such as weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), Cox analysis, and least absolute shrinkage and selection operator (LASSO) analysis were performed. Results:  According to PMT scores, we confirmed that PMT status was positively associated with risky behaviors and poor prognosis in glioma. The 149 PMT-related lncRNAs were identified by WGCNA analysis, among which 10 (LINC01057, TP73-AS1, AP000695.4, LINC01503, CRNDE, OSMR-AS1, SNHG18, AC145343.2, RP11-25K21.6, RP1138L15.2) with significant prognostic value were further screened to construct a PMT-related lncRNA risk signature, which could divide cases into two groups with distinct prognoses. Multivariate Cox regression analyses indicated that the signature was an independent prognostic factor for high-grade glioma. High-risk cases were more likely to be classified as the mesenchymal subtype, which confers enhanced immunosuppressive status by recruiting macrophages, neutrophils, and regulatory T cells. Moreover, six lncRNAs of the signature could act as competing endogenous RNAs to promote PMT in glioblastoma. Conclusions:  We profiled PMT status in glioma and established a PMT-related 10-lncRNA signature for glioma that could independently predict glioma survival and trigger PMT, which enhanced immunosuppression. Keywords:  Glioma, PMT, lncRNA, Prognosis, ceRNA network, Immune

*Correspondence: [email protected]; [email protected] 1 Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang 110001, Liaoning, China Full list of author information is available at the end of the article

Background Glioma is the most common primary brain tumor, and despite great improvements in the treatment modalities for glioma, including surgery, radiotherapy and chemotherapy, patients with glioma, especially glioblastoma multiforme (GBM), still have unfavorable outcomes [1, 2]. To explore more effective treatments, molecular subtypes related to GBM prognosis have been identified based on large genomic data. Rece