基于生物信息学分析胃癌双微体中增强子的调控机制

doi:10.16288/j.yczz.24-291

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Hereditas(Beijing) ›› 2025, Vol. 47 ›› Issue (5): 558-572.doi: 10.16288/j.yczz.24-291

• Research Article • Previous Articles Next Articles

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

Mengting An¹^,²(), Guanlin Guo¹^,²(), Jie Wu¹^,², Wenjing Sun¹^,², Xueyuan Jia¹^,²()

1. Department of Medical Genetics, School of Bastic Medical Sciences, Harbin Medical University, Harbin 150081, China
2. Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin 150081, China

Received:2024-12-17 Revised:2025-02-04 Online:2025-02-10 Published:2025-02-10
Contact: Xueyuan Jia E-mail:anmenting814@163.com;ggl950913@163.com;jiaxueyuan@hrbmu.edu.cn
Supported by:
Natural Science Foundation of Heilongjiang Province of China(JQ2022C004);Joint Guiding Project of Heilongjiang Natural Science Foundation(LH2021H006);HMU Marshal Initiative Funding(HMUMIF-21007)

Abstract

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.

Key words: double minute chromosomes, enhancer, gastric cancer, tumor immunity, tumor drug resistance, bioinformatics

Mengting An, Guanlin Guo, Jie Wu, Wenjing Sun, Xueyuan Jia. Analysis of regulatory mechanisms of enhancers in gastric cancer with double minute chromosomes based on bioinformatics[J]. Hereditas(Beijing), 2025, 47(5): 558-572.

Figures/Tables 11

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

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