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Integrated microenvironment-associated genomic profiles identify LRRC15 mediating recurrent glioblastoma-associated macrophages infiltration |
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| Authors: | Haichao Tang Wensi Liu Zhaoxu Xu Jianhang Zhao Weitao Wang Zhaojin Yu Minjie Wei |
| Institution: | 1. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China
Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, Liaoning Cancer immune peptide drug Engineering Technology Research Center;2. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumours, Ministry of Education, China Medical University, Shenyang, China Contribution: Conceptualization (equal), Data curation (lead), Formal analysis (lead), Methodology (equal), Writing - original draft (lead);3. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumours, Ministry of Education, China Medical University, Shenyang, China Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal);4. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumours, Ministry of Education, China Medical University, Shenyang, China Contribution: Data curation (supporting), Formal analysis (equal);5. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumours, Ministry of Education, China Medical University, Shenyang, China Contribution: Formal analysis (supporting), Methodology (supporting), Visualization (supporting);6. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumours, Ministry of Education, China Medical University, Shenyang, China Contribution: Data curation (supporting), Validation (supporting);7. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China |
| Abstract: | Glioblastoma (GBM) is the most common malignant intracranial tumour with intrinsic infiltrative characteristics, which could lead to most patients eventually relapse. The prognosis of recurrent GBM patients remains unsatisfactory. Cancer cell infiltration and their interaction with the tumour microenvironment (TME) could promote tumour recurrence and treatment resistance. In our study, we aimed to identify potential tumour target correlated with rGBM microenvironment based on the gene expression profiles and clinical information of rGBM patients from The Cancer Genome Atlas (TCGA) database. LRRC15 gene with prognostic value was screened by univariate and multivariate analysis, and the correlation between macrophages and LRRC15 was identified as well. Furthermore, the prognosis correlation and immune characteristics of LRRC15 were validated using the Chinese Glioma Genome Atlas (CGGA) database and our clinical tissues by immunochemistry assay. Additionally, we utilized the transwell assay and carboxy fluorescein succinimidyl ester (CFSE) tracking to further confirm the effects of LRRC15 on attracting microglia/macrophages and tumour cell proliferation in the TME. Gene profiles-based rGBM microenvironment identified that LRRC15 could act in collusion with microglia/macrophages in the rGBM microenvironment to promote the poor prognosis, especially in mesenchymal subtype, indicating the strategies of targeting LRRC15 to improve macrophages-based immunosuppressive effects could be promising for rGBM treatments. |
| Keywords: | immunology LRRC15 macrophages recurrent glioblastoma tumour microenvironment |