Identification of a single cell-based signature for predicting prognosis risk and immunotherapy response in patients with glioblastoma

Ziyu Dai; Nan Zhang; Ran Zhou; Hao Zhang; Liyang Zhang; Zeyu Wang; Wenjing Zeng; Peng Luo; Jian Zhang; Zhixiong Liu; Quan Cheng

doi:10.1016/j.clim.2023.109345

Identification of a single cell-based signature for predicting prognosis risk and immunotherapy response in patients with glioblastoma

Clin Immunol. 2023 Jun:251:109345. doi: 10.1016/j.clim.2023.109345. Epub 2023 Apr 24.

Authors

Ziyu Dai¹, Nan Zhang², Ran Zhou³, Hao Zhang¹, Liyang Zhang⁴, Zeyu Wang¹, Wenjing Zeng⁵, Peng Luo⁶, Jian Zhang⁶, Zhixiong Liu⁷, Quan Cheng⁸

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China.
² Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410078, China; One-Third Lab, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150088, China.
³ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China; Division of Neuroscience, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK.
⁴ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China; Clinical Diagnosis and Therapeutic Center of Glioma, Xiangya Hospital, Central South University, Changsha 410078, China.
⁵ Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410078, China.
⁶ Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China.
⁷ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China. Electronic address: zhixiongliu@csu.edu.cn.
⁸ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China; Clinical Diagnosis and Therapeutic Center of Glioma, Xiangya Hospital, Central South University, Changsha 410078, China. Electronic address: chengquan@csu.edu.cn.

PMID: 37100336
DOI: 10.1016/j.clim.2023.109345

Abstract

This study constructed a novel gene pair signature based on bulk and single-cell sequencing samples in relative expression order within the samples. The subsequent analysis included glioma samples from Xiangya Hospital. Gene pair signatures possessed a solid ability to predict the prognosis of glioblastoma and pan-cancer. Samples having different malignant biological hallmarks were distinguished by the algorithm, with the high gene pair score group featuring classic copy number variations, oncogenic mutations, and extensive hypomethylation, mediating poor prognosis. The increased gene pair score group with a poorer prognosis demonstrated significant enrichment in tumor and immune-related signaling pathways while presenting immunological diversity. The remarkable infiltration of M2 macrophages in the high gene pair score group was validated by multiplex immunofluorescence, suggesting that combination therapies targeting adaptive and innate immunity may serve as a therapeutic option. Overall, a gene pair signature applicable to predict prognosis hopefully provides a reference to guide clinical practice.

Keywords: Glioblastoma; Pan-cancer; Prognostic signature; Single-cell RNA sequencing; Tumor immunotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Copy Number Variations
Glioblastoma* / genetics
Glioblastoma* / therapy
Glioma*
Humans
Immunotherapy
Prognosis