Chemosensitivity of gastric cancer: analysis of key pathogenic transcription factors

We aimed to screen the key pathogenic transcription factors of gastric cancer and analyzed the correlation between the expression of transcription factors and chemotherapy drugs in gastric cancer.

Gastric cancer RNA sequencing data sets, single nucleotide polymorphism data sets, and corresponding clinical data sets were downloaded from The Cancer Genome Atlas, which is public data. The expression of transcription factors in gastric cancer and normal tissues was analyzed with R software. Pathway enrichment analysis of differentially expressed transcription factors was performed using the Kyoto Encyclopedia of Genes and Genomes database. Univariate Cox analysis was used to explore the correlation between the differential expression of transcription factors and prognosis. The interaction network among differentially expressed transcription factors was constructed using String database. Spearman test was used to explore the correlation between transcription factor mutation and gene expression. The Genomics of Drug Sensitivity in Cancer database was used to examine the relationship between the expression of transcription factors and chemotherapeutic drug sensitivity.

A total of 17 differentially expressed transcription factors were screened. The results indicated that CENPA, E2F1, EMX1, HOXA9, FOXM1, and MYBL2 were prognostic risk factors for gastric cancer patients (P<0.05), while RXRG and SOX4 were prognostic protective factors for gastric cancer patients (P<0.05). FDXM1 interacted with E2F7, MYBL2, E2F1, NCAPG, and SOX9. FOXM1 gene mutation was positively correlated with the expression level (P<0.05). Based on the median value of FOXM1, the patients were divided into high expression group and low expression group of FOXM1. There was no significant difference in IC50 of 5-fluorouracil between the FOXM1 high expression group and the FOXM1 low expression group (P>0.05). The IC50 of paclitaxel in the FOXM1 high expression group was higher than that in the FOXM1 low expression group (P<0.001). The expression of IC50 of cisplatin in the FOXM1 high expression group was higher than that in the FOXM1 low expression group (P<0.05).

FOXM1 was a highly expressed transcription factor in gastric cancer. High FOXM1 expression was associated with the resistance of gastric cancer patients to paclitaxel and cisplatin. Therefore, FOXM1 is a potential therapeutic target for gastric cancer.