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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Journal of Neuroinflammation 1/2018

Molecular and clinical characterization of PTPN2 expression from RNA-seq data of 996 brain gliomas

Zeitschrift:
Journal of Neuroinflammation > Ausgabe 1/2018
Autoren:
Peng-fei Wang, Hong-qing Cai, Chuan-bao Zhang, Yan-Michael Li, Xiang Liu, Jing-hai Wan, Tao Jiang, Shou-wei Li, Chang-Xiang Yan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12974-018-1187-4) contains supplementary material, which is available to authorized users.
Peng-fei Wang, Hong-qing Cai, and Chuan-bao Zhang contributed equally to this work.
Peng-fei Wang, Hong-qing Cai, and Chuan-bao are co-first authors.

Abstract

Background

Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling.

Methods

Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas. RNA-seq data of a cohort of 325 patients with glioma were available from the Chinese Glioma Genome Atlas and 671 from The Cancer Genome Atlas. R language, GraphPad Prism 5, and SPSS 22.0 were used to analyze data and draw figures.

Results

PTPN2 transcript levels increased significantly with higher grades of glioma and in isocitrate dehydrogenase (IDH) wild-type and mesenchymal subtype gliomas. A comprehensive biological analysis was conducted, which indicated a crucial role of PTPN2 in the immune and inflammation responses in gliomas. Specifically, PTPN2 was positively associated with HCK, LCK, MHC II, and STAT1 but negatively related to IgG and interferon. Moreover, canonical correlation analysis showed a positive correlation of PTPN2 with infiltrating immune cells, such as macrophages, neutrophils, and CD8+ T cells. Clinically, higher levels of PTPN2 were associated with a worse overall survival both in patients with gliomas and glioblastomas.

Conclusion

PTPN2 expression level was increased in glioblastomas and associated with gliomas of the IDH wild-type and mesenchymal subtype. There was a close correlation between PTPN2 and the immune response and inflammatory activity in gliomas. Our results show that PTPN2 is a promising immunotherapy target and may provide additional treatment strategies.
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