Ferroptosis Activation Scoring Model Assists in Chemotherapeutic Agents’ Selection and Mediates Cross-Talk With Immunocytes in Malignant Glioblastoma

Frontiers in Immunology

Immunology

Binyuan Xu¹  Lifu Zheng¹  Xisong Liang²  Kui Yang²  Xun Zhang²  Hao Zhang²  Fan Fan²  Zeyu Wang³  Ziyu Dai³  Zhixiong Liu⁴  Quan Cheng⁵ 

[1] Clinic Medicine of 5-Year Program, Xiangya School of Medicine, Central South University, Changsha, China;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China;Clinical Diagnosis and Therapy Center for Gliomas of Xiangya Hospital, Central South University, Changsha, China;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China;Clinical Diagnosis and Therapy Center for Gliomas of Xiangya Hospital, Central South University, Changsha, China;Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China;

关键词: ferroptosis;    glioblastoma;    mesenchymal;    immunocytes;    cell–cell communication;   

DOI  :  10.3389/fimmu.2021.747408

 received in 2021-07-26, accepted in 2021-11-04,  发布年份 2022

来源: Frontiers

【 摘 要 】

Gliomas are aggressive tumors in the central nervous system and glioblastoma is the most malignant type. Ferroptosis is a programmed cell death that can modulate tumor resistance to therapy and the components of tumor microenvironment. However, the relationship between ferroptosis, tumor immune landscape, and glioblastoma progression is still elusive. In this work, data from bulk RNA-seq analysis, single cell RNA-seq analysis, and our own data (the Xiangya cohort) are integrated to reveal their relationships. A scoring system is constructed according to ferroptosis related gene expression, and high scoring samples resistant to ferroptosis and show worse survival outcome than low scoring samples. Notably, most of the high scoring samples are aggressive glioblastoma subtype, mesenchymal, and classical, by calculating RNA velocity. Cross-talk between high scoring glioblastoma cells and immunocytes are explored by R package ‘celltalker’. Ligand–receptor pairs like the TRAIL or TWEAK signaling pathway are identified as novel bridges implying how ferroptosis modulate immunocytes’ function and shape tumor microenvironment. Critically, potential drugs target to high scoring samples are predicted, namely, SNX2112, AZ628, and bortezomib and five compounds from the CellMiner database. Taken together, ferroptosis associates with glioblastoma aggressiveness, cross-talk with immunocytes and offer novel chemotherapy strategy.

【 授权许可】

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Copyright © 2022 Wang, Dai, Zheng, Xu, Zhang, Fan, Zhang, Liang, Liu, Yang and Cheng