Research Paper Volume 15, Issue 19 pp 10785—10810

PD-L1-related IncRNAs are associated with malignant characteristics and immune microenvironment in glioma

Zhiwei Xia1, *, , Ruxin Tu2,4, *, , Fangkun Liu3, , Hao Zhang3,5, , Ziyu Dai3, , Zeyu Wang3,6, , Peng Luo7, , Shiqing He8, , Gelei Xiao3, , Jie Feng2,4,9, , Quan Cheng3,4, ,

  • 1 Department of Neurology, Hunan Aerospace Hospital, Changsha 410205, Hunan, P.R. China
  • 2 Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
  • 3 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
  • 4 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P.R. China
  • 5 Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China
  • 6 MRC Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Little France, Edinburgh, EH16 4UU, UK
  • 7 Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, P.R. China
  • 8 Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, P.R. China
  • 9 Hunan Clinical Research Center for Cerebrovascular Disease, Changsha 410008, Hunan Province, P.R. China
* Equal contribution and shared first authorship

Received: March 14, 2023       Accepted: August 21, 2023       Published: October 12, 2023      

https://doi.org/10.18632/aging.205120
How to Cite

Copyright: © 2023 Xia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: The expression of long non-coding RNA (lncRNA) can function as diagnostic and therapeutic biomarker for tumors. This research explores the role of PD-L1-related lncRNAs in affecting malignant characteristics and the immune microenvironment of glioma.

Methods: Downloading gene expression profiles and clinicopathological information of glioma from TCGA and CGGA databases, 6 PD-L1-related lncRNAs were identified through correlation analysis, Cox and LASSO regression analysis, establishing the risk score model based on them. Bioinformatics analysis and cell experiments in vitro were adopted to verify the effects of LINC01271 on glioma.

Results: Risk scores based on 6 PD-L1-related lncRNAs (AL355974.3, LINC01271, AC011899.3, MIR4500HG, LINC02594, AL357055.3) can reflect malignant characteristics and immunotherapy response of glioma. Patients with high LINC01271 expression had a worse prognosis, a higher abundance of M1 subtype macrophages in the immune microenvironment, and a higher degree of tumor malignancy. Experiments in vitro confirmed its positive regulatory effect on the proliferation and migration of glioma cells.

Conclusions: The risk score model based on 6 PD-L1-related lncRNAs can reflect the malignant characteristics and prognosis of glioma. LINC01271 can independently be used as a new target for prognosis evaluation and therapy.

Abbreviations

LncRNA: Long non-coding RNAs; TCGA: The Cancer Genome Atlas; CGGA: Chinese Glioma Genome Atlas; TIDE: Tumor immune dysfunction and exclusion; GDSC: Genomics of Drug Sensitivity in Cancer; LASSO: Least Absolute Shrinkage and Selection Operator; GSVA: Gene set variation analysis; GO: Gene ontology; CCK-8: Cell counting kit-8; EdU: 5-Ethynyl-2’-deoxyuridine; Rt-qPCR: Real-time polymerase chain reaction; PCA: Principal component analysis; LGG: Lower-grade gliomas; GBM: Glioblastomas; WHO: World Health Organization; OS: Overall Survival; DSS: Disease-Specific Survival; PFI: Progression-Free Interval; ICI: Immune checkpoint inhibitors; PD-1/ PDCD1: Programmed cell death protein 1; PD-L1: Programmed cell death ligand-1; CTLA-4: Cytotoxic T lymphocyte antigen 4; HAVCR2: Hepatitis A virus cellular receptor 2; IDO1: Indolamine 2,3-dioxygenase 1; LAG3: Lymphocyte activation gene 3; MGMT: O6-methylguanine-DNA-methyltransferase; IDH: Isocitrate dehydrogenase; ROC: Receiver operating curve; AUC: Area under curve; TMZ: Temozolomide; TIME: Tumor immune microenvironment; TMB: Tumor mutation burden; TAM: Tumor-associated macrophages; PFS: Progression-free survival; IC50: Half-maximal inhibitory concentration; BBB: Blood-brain barrier; HR: Hazard ratio; APM: Antigen-processing machinery; NE: Neural: PN: Proneural: CL: Classical: MES: Mesenchymal; NSCLC: non-small cell lung cancer; E2Fs: E2F transcription factors; CDK: Cyclin-dependent kinase; RB: Retinoblastoma.