STING is significantly increased in high-grade glioma with high risk of recurrence

Title : STING is significantly increased in high-grade glioma with high risk of recurrence

Abstract:

To our knowledge, the potential relationships among the frequently mutated genes, well-known homologous recombination repair (HRR) proteins, and immune proteins in glioma from a clinical perspective have not been explored. Here, a total of 126 surgical tissues from patients initially diagnosed with glioma were included. The genetic alterations were tested using the targeted next-generation sequencing technique. The expression of HRR proteins, immune proteins, and genetic alteration-related proteins were detected using immunostaining. Integrated analysis showed that ATRX is positively correlated with STING in high-grade glioma (HGG) with wild-type ATRX and IDH1. Then, a relapse predictive risk-scoring model was established using the least absolute shrinkage and selection operator regression algorithms. The scores based on the expression of ATRX and STING significantly predict the recurrence for glioma patients, which further predict the survival for specific subgroups, characterized with high expression of RAD51 and wild-type TERT. Moreover, STING is significantly higher in patients with high relapse risk. Interestingly, STING inhibitors and agonists both suppress the growth of HGG cells, regardless of their STING levels and STING pathway activity, whereas RAD51 inhibitor B02 is found to exclusively sensitize HGG cells with high expression of STING to temozolomide in vitro and in vivo. Overall, findings in the study not only reveal that ATRX is closely correlated with STING to drive the relapse of HGG, but also provide a STING-guided combined strategy to treat patients with aggressive gliomas. Translation of these findings will ultimately improve the outcomes for ATRX and IDH1 genomically stratified subgroups in HGG.

Biography:

Dr. Qingyuan Yang studied Clinical Laboratory Diagnostics at the Tongji University, Shanghai, China and graduated as MD in 2014. She then worked in Shanghai Tenth People’s Hospital as a technician in charge in the department of molecular diagnostics during 2014 to 2018. Afterwards, she joined Dr. Willers Henning and Miyamoto David lab as a senior postdoctoral fellow in Massachusetts General Hospital of Harvard University School of Medicine, USA, during 2019 to 2021. She gained a position of a technician deputy director in Department of Pathology, Shanghai Ninth People’s Hospital of Shanghai Jiaotong University School of Medicine. She is now focusing on elaborating the underlying mechanisms of spatially targeted STING in the treatment of GBM and developing new strategies to precisely deliver its agonists without adverse events.