_applied_  
_sciences_  
_Article_  
**Bioinformatics Characterization of Candidate Genes Associated with Gene Network and miRNA Regulation in Esophageal Squamous Cell Carcinoma Patients**  
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Footnote 1: [[https://www.mdpi.com/journal/applsci](https://www.mdpi.com/journal/applsci)]([https://www.mdpi.com/journal/applsci](https://www.mdpi.com/journal/applsci))  
FootnoteIt has been recognized that ESCA has various histological subtypes, the most common of which are esophageal adenocarcinoma (AC), esophageal squamous cell carcinoma (ESCC), and small cell carcinoma (SCC) [5]. The squamous cell carcinoma is the most frequent epithelial malignancy of the esophageal [6; 7]. Despite continual advancements in the use of surgeries, radiation, chemotherapy, targeted therapy, immunotherapy, and anticancer drugs in the holistic treatment of cancer, the 5-year mortality rate is less than 10% globally [8; 9; 10; 11]. The molecular mechanism underlying the incidence and progression of ESCC has yet to be fully understood [12]. Therefore, it is urgent to explore novel biomarkers for diagnosis, prognosis, and development of new anti-cancer drugs for ESCC susceptible individuals. Although, deep processing of publicly accessible genomic data to find new and unique gene predictive signals can help patients with prognostic classification and tailored treatment. Presently, one of the primary goals of ESCC research is to find essential genes or particular biomarkers. It influences the onset and progression of ESCC to identify genetic and epigenetic risk factors and better understand their possible underlying molecular mechanism [12; 13; 14]. Epigenetics is the study to describe any heritable change in gene expression that is not associated with a difference in the chromosomal DNA sequence [15; 16; 17]. The most prevalent epigenetic modification is DNA methylation, linked to gene expression regulation, fetal development, specific gene inactivation, genomic integrity, genomic imprinting, and cell proliferation [18; 19; 20]. DNA methylation of genes at the promoter region is linked to the silence of essential genes, including oncogenes and tumor suppressors, and is considered a cornerstone of many malignancies [21; 22; 23]. Even though several researchers have demonstrated that specific genes with aberrant DNA hyper or hypomethyllation are involved in various stages of ESCC development, determining the complete profile and mechanisms of the interaction network remains problematic [24; 25; 26]. In this pertain, we have predicted methylation at the promoter region for the top ten hub genes (HGsT10). The ability to accurately identify and characterize the metabolic pathway from the identified hub genes that regulate the biological processes related to ESCC is essential. It may be provided by implementing an extensive assessment of numerous datasets. This perspective identifies the biological process, molecular function, and metabolic pathway of hub genes/oncogenes using the WebGestalt toolkit to understand the underlying interactive mechanisms extensively. Likewise, [PERSON] et al. predicted the prognostic marker and hub genes by analyzing the hepatocellular and gynecological carcinoma TCGA samples. The study's outcome stated that it might be helpful in personalized therapy to decide medical practice [27; 28]. [PERSON] et al. also described that identifying signature genes in ovarian cancer patients' samples is vital as potential therapeutic targets [29]. [PERSON] et al. determined that the vital role of hub genes in the progression of head and neck cancer might be used to invent the novel diagnostic method and treatment [30]. However, no extensive investigation has been conducted to determine the mutational essentiality and its impact on the overall survival rate of ESCC patients [31; 32]. We integrated genome-wide DNA methylation and gene expression data to find DNA methylation indicators for early ESCC diagnosis.