Cancer Genetics and Epigenetics, 2025, Vol.13, No.2, 62-76 http://medscipublisher.com/index.php/cge 65 developmental abnormalities or EAC, changes in the TP53 gene were more common, which means that these genetic changes were alterations that occurred earlier in the process of chromosomal instability in EAC (Stachler et al., 2018). 4.2 The role of copy number changes in tumor development Copy number changes (CNVs) are a characteristic of EAC and play a key role in the process of tumor development. Comparative genomic analysis revealed that compared with patients who responded to treatment, those who did not respond to neoadjuvant chemotherapy (NAC) had a higher degree of chromosomal instability and more CNVs. Some specific CNVs, involving genes controlling cell division (such as CDKN2A, CCND1), c-Myc (MYC), RTK/PIK3 signaling (KRAS, EGFR), and gastrointestinal cell differentiation (GATA6) pathways, are associated with NAC resistance (Izadi et al., 2021). After comprehensive genetic testing, many patients with esophageal adenocarcinoma (EAC) were found to have gene copy number variations (CNVs). Among them, genes like ANO1 are significantly associated with poor treatment outcomes for patients. The ANO1 gene activates the TGF-β signaling channel, promoting the continuous growth of tumors. In laboratory experiments and animal experiments, if measures are taken to reduce the activity of this gene, tumor growth can be inhibited (Yu et al., 2019). Multi-faceted molecular studies have also shown that alterations in gene copy number, combined with changes in DNA methylation, can significantly affect the gene activity of EAC. This also indicates that gene copy number variations play a key role in the molecular characteristics of this disease (Peng et al., 2017). Overall, chromosomal abnormalities and variations in gene copy numbers are the main factors causing instability of the EAC gene and triggering tumors. Understanding these genetic changes can help us figure out the causes of EAC and also assist us in identifying potential targets that may improve the treatment outcomes for patients. 5 Genomic Pathways of the Pathogenesis of EAC 5.1 Cell cycle regulation Cell cycle regulation is very crucial in the pathogenesis of esophageal adenocarcinoma (EAC). Once there is a problem with the cell cycle control, cells will proliferate unrestrainedly in large quantities, which is precisely one of the typical characteristics of cancer. Some studies have pointed out that the expression of deoxyribonuclease, especially APE1, is related to the genetic instability of EAC. In EAC cell samples, after inhibiting the effect of APE1, the cell division process stagnated and growth was also affected, indicating that it plays a role in regulating cell division and promoting tumor formation (Kumar et al., 2023). In addition, through comprehensive network analysis, it was found that the abnormally expressed genes in EAC were related to the processes of cell division and replication, which further demonstrated the importance of cell cycle regulation in the pathogenesis of EAC (Nangraj et al., 2020). 5.2 Pathways of apoptosis and cell survival The process of cell apoptosis and survival is crucial for ensuring the normal operation of cells and preventing the occurrence of tumors. In esophageal adenocarcinoma (EAC), the two signal transduction pathways, transforming growth factor -β (TGFB) and Jun N-terminal kinase (JNK), become overly active. It is known that these two pathways regulate the genes that affect cell survival and apoptosis. If the transmission of TGFB or JNK signals is blocked in EAC cells, the proliferation rate of the cells will significantly slow down and the mobility ability will also decline. This indicates that these pathways help EAC cells survive and develop (Blum et al., 2019). In addition, Toll-like receptor (TLR) pathways, especially after mutations in TLR4, can disrupt the body's own immune signal transmission and create an environment suitable for tumor growth. This also demonstrates the role of immune-related pathways in the survival and apoptosis of EAC cells (Elliott et al., 2017). 5.3 DNA repair mechanism The DNA repair mechanism is indispensable for maintaining the stability and integrity of genes. In EAC, once the DNA repair pathway is disrupted, it will cause gene instability and accelerate the development of cancer. Studies have shown that an increase in APE1 content can disrupt the normal order of homologous recombination (HR) and the cell cycle, promoting genetic changes in EAC and tumor formation. Inhibition of APE1 weakens the
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