Article link: https://doi.org/10.1016/j.gendis.2024.101431

The paper entitled “Systematic Pan-Cancer Analysis Identifies DNASE2 as a Potential Prognostic Marker and Immunotherapeutic Target for Glioblastoma Multiforme”, researched by the team of Professor Xiao Xinru at the Center for Skull Base and Brain Tumor of the Department of Neurosurgery at Xuanwu Hospital, was published online in Genes & Diseases on September 10, 2024. (IF=6.9, JCR Zone 1)

Keywords: Glioblastoma (GBM), Deoxyribonuclease 2 (DNASE2)

This study is the first to discover the key role of deoxyribonuclease 2 (DNASE2) in the proliferation, migration, invasion and immune microenvironment of glioblastoma (GBM) and its regulatory mechanism. DNASE2 is closely related to tumor proliferation and apoptosis, innate immune signal transduction, chronic inflammation and systemic autoimmune inflammatory diseases. However, the role of DNASE2 in GBM and its mechanism remain unclear.

In this study, we analyzed the differential expression and prognostic relevance of DNASE2 mRNA in 31 tumor and normal tissues based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases. The results showed that DNASE2 expression was significantly elevated in GBM patients, and its expression was negatively correlated with the overall survival (OS) and progression-free survival (PFS) of GBM patients. Downregulating DNASE2 expression can reduce the proliferation, migration and invasion of GBM cells. Further studies have found that the function of DNASE2 is related to the immune microenvironment of GBM patients, and silencing DNASE2 can regulate the immune activity of GBM through the IL-17 signaling pathway, Notch signaling pathway, Toll-like receptor signaling pathway, and SPP1 and S100A8/9 genes, thereby reducing the proliferation, migration, and invasion of GBM cells. In summary, the expression level of DNASE2 is elevated in GBM patients and affects the development of GBM through multiple immune-related pathways. Therefore, DNASE2 may be used as a potential prognostic biomarker and therapeutic target for glioblastoma.

Co-corresponding author

Xiao Xinru

Director of the Skull Base and Brain Tumor Center, Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, PhD, Senior Consultant Neurosurgeon, Professor

He is the Director of the Skull Base and Brain Tumor Center, Department of Neurosurgery, Xuanwu Hospital; Chairman of the Neuroanatomy Branch of the Chinese Anatomy Society, Vice Chairman and Secretary-General of the Cranial Base Surgery Branch of the European and American Medical Association, Director of the European and American Medical Association, Standing Committee Member of the Neuroendoscope and Minimally Invasive Medicine Committee of the China Medicine Education Association, Member of the Skull Base Surgery Group of the Continuing Education Neurosurgery Branch of the National Health Commission, Recipient of the “National Famous Doctor” award. He has published more than 10 papers in journals including the Journal of Neurosurgery; presided over 4 projects including key projects of the Beijing Natural Science Foundation, and authorized 3 invention patents.

Clinic information

Monday morning, Monday afternoon

Co-corresponding author

Cheng Ye

Xuanwu Hospital, Capital Medical University

Department of Neurosurgery Consultant Neurosurgeon, Associate Professor

Master's Supervisor; Deputy Secretary of the First Party Branch of the Neurosurgery Department of Xuanwu Hospital; Secretary of the Medical Department of the National Medical Center for Neurological Diseases (Xuanwu). He is a Member of the Neuro-Oncology Branch of the Chinese Neuroscience Society, Member of the Skull Base Surgery Branch of the European and American Medical Association, Member of the Neurosurgery Branch of the Chinese Anatomy Association, Member of the Youth Committee of the Continuing Education Neurosurgery Branch of the National Health Commission, and Young Scientist of the Chinese Medical Doctor Association for Brain Glioma. He has got the First Prize in the National Neurosurgery Diagnosis and Treatment Competence Competition of the National Health Commission. He is an eight-year, Harvard Medical School co-trained PhD from Baikoun Medical School of Jilin University. He has presided over national natural science projects, youth funds, Beijing Science and Technology Rising Stars, the Beijing Medical Management Center's “Innovation DreamWorks”, and is the recipient of an outstanding doctoral thesis in Jilin Province. Xuanwu Hospital has hired him as a “talent pool”. He has published more than 20 SCI articles as the first or corresponding author, with a total IF of more than 100 points and nearly 900 total citations. His representative works have been published in journals such as BMC medicine, Eur J Nucl Med Mol Imaging, Cancer letters, and Genes and Diseases. Authorized 2 national invention patents (first inventor).

Clinic information

Tuesday afternoon

Co-corresponding author

Li Shichao

Hebei Medical University Second Hospital

Supervising technician

She is an attending physician and research assistant commissioner at the Infection Diagnosis Center of Hebei Medical University Second Hospital. She graduated with a doctorate in pathophysiology from Hebei Medical University and is the recipient of Hebei Province's Outstanding Doctoral Dissertation Award. Her main research interests are the pathophysiological basis and applied research of nerve damage. She has published 6 journal papers in journals including Molecular Neurobiology and Genes and Diseases.

Co-first author

Cao Jun

Department of Neurosurgery, Rizhao People's Hospital

Attending Neurosurgeon Master of Medicine

He is a graduate Xuanwu Hospital of Capital Medical University Specialized Training. He is a Member Shandong Provincial Rehabilitation Medical Association, Consciousness Disorders and Promotion of Wakefulness Branch. She has been engaged in clinical medicine, research and teaching for more than 10 years. Specialties: minimally invasive surgical treatment of various intracranial and spinal tumors, as well as trigeminal neuralgia and facial spasm. He has published 5 articles in Chinese core journals and SCI as the first or co-first author, and has co-authored 3 books.

Co-first author

Chen Si

Department of Neurosurgery, Tangshan People's Hospital

Attending Neurosurgeon Master of Medicine

He is a trainee of Xuanwu Hospital of Capital Medical University Specialized Training Class 2021 .He has engaged in clinical medicine, scientific research and teaching for more than 10 years. Specialties: various intracranial tumors, traumatic brain injury, cerebrovascular disease. He published 3 articles in Chinese core journals and SCI as the first or co-author.