Objective: Recurrent high-grade glioma presents the worst prognosis among brain tumors. Given that most high-grade gliomas recur after a standard surgery and radiochemotherapy, new treatment modalities are needed. CHA displays regulatory, antitumor and immunoregulatory bioactivities in animals and cultured human tumor cells. This study aimed to explore the antitumor mechanism of CHA in patients with recurrent highgrade glioma by high-throughput RNA-sequencing (RNA-seq).

Methods: A case series with six patients was included. Their peripheral blood samples were collected two times (pretreatment and day 15) during CHA therapy. RNA-seq was used to sequence transcriptomes. The differentially expressed genes (DEGs) detected by MATLAB software were used to conduct Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology functional analyses.

Results: Two patients (P3 and P4) achieved stable disease state after CHA therapy, while the tumors progressed in the other four patients. The progression-free survival times of P3 and P4 were 8.1 and 4.9 months, respectively. The overall survival time of both patients was 16.7 months, and these patients are still alive to date. P3 and P4 showed the least average fold changes in total DEGs among the six patients. A total of 269 and 182 commonly upregulated and downregulated DEGs were identified in P3 and P4, respectively. These genes were enriched with significant signal pathways or gene terms related to immune system. Gene expression levels from these pathways or terms were upregulated or downregulated uniformly in P3 and P4, which was significantly different from the results in other patients.

Conclusions: This study presented evidence about the immunomodulation function of CHA in patients with recurrent high-grade glioma. In CHA responsive patients, CHA may change the gene expression and upregulate the immune system activity to inhibit tumor development, thereby making it a potential antitumor drug.

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