Potential targets for synergistic bipolar irreversible electroporation in tumor suppression through transcriptomics and proteomics analysis

Abstract

Previous studies have demonstrated that synergistic bipolar irreversible electroporation (SBIRE) is a promising non-thermal tumor ablation technique that effectively targets tumors without causing muscle contractions. Despite its clinical potential, the mechanistic understanding of SBIRE’s tumor-suppressive effects remains underexplored. This study aims to identify potential molecular targets for SBIRE-mediated tumor suppression through comprehensive transcriptomics and proteomics analyses. Mice were selected as subjects for the creation of tumor models by the subcutaneous tumor-bearing method. Following the SBIRE intervention, tumor surveillance and pathological investigations were carried out. A comprehensive investigation was conducted using RNA sequencing-based transcriptomics and label-free quantitative proteomics to examine normal and SBIRE treated tumor samples. Differentially expressed genes (DEGs) and crucial signaling pathways were found using bioinformatics analysis. Western blot (WB), immunohistochemistry (IHC), and quantitative real-time PCR (qRT-PCR) were used to validate potentially associated genes. The results demonstrate that a substantial reduction in tumor size was achieved following SBIRE treatment. A total of 86 genes exhibited differential expression in tumors, with 84 genes showing upregulation and 2 genes showing downregulation. According to bioinformatics research, these DEGs were involved in a wide variety of biological activities, such as cell adhesion, positive regulation of tumor necrosis factor production, and immune system process. Beside major enrichment pathways like Efferocytosis, Endocytosis, PPAR signaling pathway and Metabolic pathways. The upregulation of WDFY family member 4 (WDFY4), Thrombospondin 1(THBS1), Pentraxin 3 (PTX3), Superoxide dismutase 3 (SOD3) and Glutathione peroxidase 3 (GPX3) genes were confirmed. These insights into the molecular underpinnings of SBIRE offer a novel therapeutic strategy for enhancing tumor suppression and improving clinical outcomes in cancer treatment.