Article Abstract

First-in-human immunomodulation mechanism research of chlorogenic acid in patients with recurrent high-grade glioma

Authors: Shoubo Yang , Zhuang Kang , Ping Li, Lin Feng , Kaidi Gao , Xiaosong Zhong , Shujun Cheng ,Wenbin Li


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.
Chlorogenic acid (CGA) displays regulatory, antitumor and immunoregulatory bioactivities in animals and cultured
human tumor cells. This study aimed to explore the antitumor mechanism of CGA in patients with recurrent high-
grade 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 CGA 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 CGA 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 CGA in patients with
recurrent high-grade glioma. In CGA responsive patients, CGA may change the gene expression and upregulate
the immune system activity to inhibit tumor development, thereby making it a potential antitumor drug.
Keywords: Chlorogenic acid; glioma; therapy; RNA-sequencing

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