Comprehensive analysis to evaluate the molecular biological mechanism and clinical efficacy of Jian Pi Yang Zheng Xiao Zheng in the treatment of gastric cancer

Abstract

BackgroundClinically, Jian Pi Yang Zheng Xiao Zheng (JPYZXZ) has been used for many years to treat gastric cancer (GC); however, the underlying mechanism and targets are still undetermined. MethodsThe active JPYZXZ components were assessed by Liquid chromatography combined with quadrupole-orbitrap high-resolution mass spectrometry (LC-Q-orbitrap-HRMS). These findings were combined with the TCM Systematic Pharmacology Database and Analysis Platform (TCMSP) database to perform network pharmacological analysis. Using second-generation sequencing on nude mouse samples and single-cell sequencing on human GC tissue, we investigated the potential targets and mechanisms of action of JPYZXZ. A multi-center clinical trial (www.chictr.org.cn ChiCTR1900028147) validated our findings. ResultsA total of 869 compounds were detected using LC-Q-orbitrap-HRMS analysis of JPYZXZ granules in order to examine the underlying mechanism of JPYZXZ in the treatment of GC. The network pharmacology analysis indicated that the potential mechanism of JPYZXZ in treating GC is associated with multiple molecular mechanisms and signaling pathways. The overlap between target genes was identified by second-generation sequencing and gene expression patterns obtained from single-cell transcriptome sequencing. We identified many crucial genes, including DZIP1, FSTL3, USP51, LHFPL6, and NREP. Subsequent investigations have consistently demonstrated that the upregulation of these genes is strongly associated with the development of an immunosuppressive microenvironment. JPYZXZ has been shown in clinical trials to reduce the number of immunosuppressive cell types in patients' peripheral blood, lower the levels of inflammatory factors, extend survival, and modify the immunosuppressive microenvironment. ConclusionsThis investigation elucidated the positive impact of multi-component, multi-target, and multi-approach JPYZXZ intervention for GC treatment.