Gene expression profiling of glioblastoma cell lines depending on TP53 status after tumor-treating fields (TTFields) treatment

• Published in: Scientific reports Vol. 10; no. 1; p. 12272
• Main Authors: Lee, Yeon-Joo, Seo, Hyun Wook, Baek, Jeong-Hwa, Lim, Sun Ha, Hwang, Sang-Gu, Kim, Eun Ho
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-07-2020; Nature Publishing Group
• Subjects: 631/67/1059/602; 692/4028/67/1059/602; Apoptosis; Biomarkers, Tumor; Brain cancer; Cell cycle; Cell Cycle - genetics; Cell death; Chemoradiotherapy; Chemotherapy; Computational Biology - methods; Electric fields; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Gene Regulatory Networks; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma - therapy; Humanities and Social Sciences; Humans; Immune response; Immune system; Inflammation; multidisciplinary; Mutation; Neoplasm Staging; p53 Protein; Prognosis; Radiation therapy; Science; Science (multidisciplinary); Transcriptome; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-68473-6

Glioblastoma is frequently associated with TP53 mutation, which is linked to a worse prognosis and response to conventional treatments (chemoradiotherapy). Therefore, targeting TP53 is a promising strategy to overcome this poor therapeutic response. Tumor-treating fields (TTFields) are a recently approved treatment for newly diagnosed glioblastoma, which involves direct application of low-intensity, intermediate-frequency alternating electric fields to the tumor, thereby offering a local tumor-killing effect. However, the influence of TP53 mutation status on the effectiveness of TTFields is controversial. Here, we identified the key gene signatures and pathways associated with TTFields in four glioblastoma cell lines varying in TP53 mutation status using gene profiling and functional annotation. Overall, genes associated with the cell cycle, cell death, and immune response were significantly altered by TTFields regardless of TP53 status. TTFields appeared to exert enhanced anti-cancer effects by altering the immune system in the inflammatory environment and regulating cell cycle- and cell death-related genes, but the precise genes influenced vary according to TP53 status. These results should facilitate detailed mechanistic studies on the molecular basis of TTFields to further develop this modality as combination therapy, which can improve the therapeutic effect and minimize side effects of chemoradiotherapy.