Combined bulk RNA-seq and single-cell RNA-seq identifies a necroptosis-related prognostic signature associated with inhibitory immune microenvironment in glioma.

Autor:	Wan S; The State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, China.; Cancer Center, Medical Research Institute, Southwest University, Chongqing, China., Moure UAE; Cancer Center, Medical Research Institute, Southwest University, Chongqing, China.; The Ninth People's Hospital of Chongqing, Affiliated Hospital of Southwest University, Chongqing, China., Liu R; The State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, China.; Cancer Center, Medical Research Institute, Southwest University, Chongqing, China., Liu C; The State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, China.; Cancer Center, Medical Research Institute, Southwest University, Chongqing, China., Wang K; The State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, China.; Cancer Center, Medical Research Institute, Southwest University, Chongqing, China., Deng L; The State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, China.; Cancer Center, Medical Research Institute, Southwest University, Chongqing, China., Liang P; Department of Neurosurgery, Chongqing Children's Hospital, Chongqing, China., Cui H; The State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing, China.; Cancer Center, Medical Research Institute, Southwest University, Chongqing, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Nov 17; Vol. 13, pp. 1013094. Date of Electronic Publication: 2022 Nov 17 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1013094
Abstrakt:	Necroptosis is a programmed cell death playing a significant role in cancer. Although necroptosis has been related to tumor immune environment (TIME) remodeling and cancer prognosis, however, the role of necroptosis-related genes (NRGs) in glioma is still elusive. In this study, a total of 159 NRGs were obtained, and parameters such as mutation rate, copy number variation (CNV), and relative expression level were assessed. Then, we constructed an 18-NRGs-based necroptosis-related signature (NRS) in the TCGA dataset, which could predict the patient's prognosis and was validated in two external CGGA datasets. We also explored the correlation between NRS and glioma TIME, chemotherapy sensitivity, and certain immunotherapy-related factors. The two necroptosis-related subtypes were discovered and could also distinguish the patients' prognosis. Through the glioblastoma (GBM) scRNA-seq data analysis, NRGs' expression levels in different GBM patient tissue cell subsets were investigated and the relative necroptosis status of different cell subsets was assessed, with the microglia score culminating among all. Moreover, we found a high infiltration level of immunosuppressive cells in glioma TIME, which was associated with poor prognosis in the high-NRS glioma patient group. Finally, the necroptosis suppressor CASP8 exhibited a high expression in glioma and was associated with poor prognosis. Subsequent experiments were performed in human glioma cell lines and patients' tissue specimens to verify the bioinformatic analytic findings about CASP8. Altogether, this study provides comprehensive evidence revealing a prognostic value of NRGs in glioma, which is associated with TIME regulation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Wan, Moure, Liu, Liu, Wang, Deng, Liang and Cui.)
Databáze:	MEDLINE
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