PMID- 33391355 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220419 IS - 1664-8021 (Print) IS - 1664-8021 (Electronic) IS - 1664-8021 (Linking) VI - 11 DP - 2020 TI - An Immune Gene-Related Five-lncRNA Signature for to Predict Glioma Prognosis. PG - 612037 LID - 10.3389/fgene.2020.612037 [doi] LID - 612037 AB - BACKGROUND: The tumor immune microenvironment is closely related to the malignant progression and treatment resistance of glioma. Long non-coding RNA (lncRNA) plays a regulatory role in this process. We investigated the pathological mechanisms within the glioma microenvironment and potential immunotherapy resistance related to lncRNAs. METHOD: We downloaded datasets derived from glioma patients and analyzed them by hierarchical clustering. Next, we analyzed the immune microenvironment of glioma, related gene expression, and patient survival. Coexpressed lncRNAs were analyzed to generate a model of lncRNAs and immune-related genes. We analyzed the model using survival and Cox regression. Then, univariate, multivariate, receiver operating characteristic (ROC), and principle component analysis (PCA) methods were used to verify the accuracy of the model. Finally, GSEA was used to evaluate which functions and pathways were associated with the differential genes. RESULTS: Normal brain tissue maintains a low-medium immune state, and gliomas are clearly divided into three groups (low to high immunity). The stromal, immune, and estimate scores increased along with immunity, while tumor purity decreased. Further, human leukocyte antigen (HLA), programmed cell death-1 (PDL1), T cell immunoglobulin and mucin domain 3 (TIM-3), B7-H3, and cytotoxic T lymphocyte-associated antigen-4 (CTLA4) expression increases concomitantly with immune state, and the patient prognosis worsens. Five immune gene-related lncRNAs (AP001007.1, LBX-AS1, MIR155HG, MAPT-AS1, and LINC00515) were screened to construct risk models. We found that risk scores are related to patient prognosis and clinical characteristics, and are positively correlated with PDL1, TIM-3, and B7-H3 expression. These lncRNAs may regulate the tumor immune microenvironment through cytokine-cytokine receptor interactions, complement, and coagulation cascades, and may promote CD8 + T cell, regulatory T cell, M1 macrophage, and infiltrating neutrophils activity in the high-immunity group. In vitro, the abnormal expression of immune-related lncRNAs and the relationship between risk scores and immune-related indicators (PDL1, CTLA4, CD3, CD8, iNOS) were verified by q-PCR and immunohistochemistry (IHC). CONCLUSION: For the first time, we constructed immune gene-related lncRNA risk models. The risk score may be a new biomarker for tumor immune subtypes and provide molecular targets for glioma immunotherapy. CI - Copyright (c) 2020 Wang, Gao, Ye, Jiang, Yang, Zhang, Wang, Zhang, Wang, Wu, Zhan, Hou, Han and Zhao. FAU - Wang, Xinzhuang AU - Wang X AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Gao, Ming AU - Gao M AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Ye, Junyi AU - Ye J AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Jiang, Qiuyi AU - Jiang Q AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Yang, Quan AU - Yang Q AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Zhang, Cheng AU - Zhang C AD - North Broward Preparatory School, Coconut Creek, FL, United States. FAU - Wang, Shengtao AU - Wang S AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Zhang, Jian AU - Zhang J AD - Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Wang, Ligang AU - Wang L AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Wu, Jianing AU - Wu J AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Zhan, Hua AU - Zhan H AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Hou, Xu AU - Hou X AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Han, Dayong AU - Han D AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. FAU - Zhao, Shiguang AU - Zhao S AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China. AD - Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China. AD - Department of Neurosurgery, The Pinghu Hospital of Shenzhen University, Shenzhen, China. LA - eng PT - Journal Article DEP - 20201216 PL - Switzerland TA - Front Genet JT - Frontiers in genetics JID - 101560621 PMC - PMC7772413 OTO - NOTNLM OT - glioma OT - immune gene sets OT - lncRNA OT - risk score OT - tumor immune microenvironment COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/01/05 06:00 MHDA- 2021/01/05 06:01 PMCR- 2020/12/16 CRDT- 2021/01/04 05:27 PHST- 2020/09/30 00:00 [received] PHST- 2020/11/09 00:00 [accepted] PHST- 2021/01/04 05:27 [entrez] PHST- 2021/01/05 06:00 [pubmed] PHST- 2021/01/05 06:01 [medline] PHST- 2020/12/16 00:00 [pmc-release] AID - 10.3389/fgene.2020.612037 [doi] PST - epublish SO - Front Genet. 2020 Dec 16;11:612037. doi: 10.3389/fgene.2020.612037. eCollection 2020.