Analysis of regulatory mechanisms of enhancers in gastric cancer with double minute chromosomes based on bioinformatics.

Abstract

Gastric cancer (GC) has a high incidence and mortality rate globally. Double minutes (DMs) are extrachromosomal circular chromosomes that carry amplified oncogenes or drug resistance genes, and they are closely associated with tumorigenesis and drug resistance. To investigate the role and regulatory mechanisms of double minutes in the malignant progression of gastric cancer, we utilize bioinformatics methods to analyze genomic copy number variation data from the CCLE cell line database and TCGA solid tumor database. We analyze and summarize the genomic features of tumor samples with double minutes. Based on these features, we classify gastric cancer samples. We use the FANTOM5 database, R package "GenomicRanges", Bedtools, and MEME SUITE to analyze the functions of the enhancers on double minutes and their regulated target genes in gastric cancer. Next, we apply the CIBERSORT package and the GDSC drug database to analyze immune cell infiltration and drug resistance in gastric cancer samples with and without double minutes from TCGA. The results show that the genome with a copy number greater than 10 and genomic fragments longer than 50 kb play a significant role. The regulatory role of double minutes enhancers affects drug resistance and tumor immunity, with disruptions in the enhancer-transcription factor-target gene regulatory loops also linked to tumor immunity. Furthermore, the target genes regulated by double minutes enhancers not only alter the expression of immune-related genes but also contribute to increased drug resistance to common chemotherapy agents in gastric cancer samples. High expression of drug resistance-related target genes in gastric cancer samples with double minutes is closely associated with poor prognosis. This study provides new insights for the treatment of gastric cancer patients with double minutes.