Potential biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) identified by WGBS

Esophageal cancer has two main clinical subtypes, including esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Unfortunately, more than half of the patients with these tumors have distal metastases at the time of diagnosis, and only ۱۰%–۲۰% of sufferers survive for ۵ years. Since ESCC is one of the major causes of cancer mortality worldwide, epigenetic origins, such as altered DNA methylation patterns, have been identified as potential tumor-factors for early detection. Thus, one of the widely used methods, whole-genome bisulfite sequencing (WGBS) analysis, has been chosen to elucidate epigenetic heterogeneity. Methods: A review was acquired by searching the databases of SpringerLink, PubMed, Nature, ScienceDirect, and ResearchGate. Results: CpG island (CGI) promoter hypomethylation and global DNA hypermethylation are two epigenetic hallmarks in cancer. Across the ESCC genome, hypermethylated regions were enriched in promoters of numerous transcription indicators and also in polycomb repressive complexes such as EZH۲/SUZ۱۲. Furthermore, about ۹۸% of CpGs were found hypomethylated, which enriched in areas with heterochromatic binding markers such as H۳K۹me۳ and H۳K۲۷me۳. WGBS also revealed that demathylated non-coding regions related to retinoid X receptor (RXR) transcription factor binding appeared to contribute to the development of ESCC. Additionally, prognostic markers have been validated in the promoter of CDC-like kinase ۱ (CLK۱), the ۳’ untranslated region of Zinc Finger E-Box Binding Homeobox ۲ (ZEB۲) and the intergenic locus surrounded by several LncRNAs. Moreover, WGBS identified some methylated regions such as Potassium Voltage-Gated Channel Subfamily A Member ۳ (KCNA۳) and Otopetrin ۲ (OTOP۲) as promising diagnostic markers for ESCC. Conclusion: It's so crucial to concentrate on early detection and begin therapy as soon as possible, especially for ESCC, which has a high mortality rate. But detecting ESCC at an early stage is challenging due to its asymptomatic characteristics, and it has a dismal prognosis with a five-year survival rate of less than ۳۰%. Therefore, this review shed light on epigenetic landscapes that shape cancer and found some important methylatoin regions as potential biomarkers of ESCC.

کلیدواژه ها:

ESCC ، Early-Detection ، Biomarkers ، WGBS ، Cancer