Identification of crucial genes associated with esophageal squamous cell carcinoma by gene expression profile analysis

Abstract

To uncover the genes associated with the development of esophageal squamous cell carcinoma (ESCC), an ESCC microarray dataset was used to identify genes differentially expressed between ESCC and normal control tissues. The dataset GSE17351 was downloaded from the Gene Expression Omnibus, containing 5 tumor esophageal mucosa samples and 5 adjacent normal esophageal mucosa samples from 5 male patients with ESCC. The differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data R package. Then, a co-expression network was constructed using the Weighted Correlation Network Analysis (WGCNA) package, and co-expression network modules were obtained with a hierarchical clustering algorithm. Additionally, functional enrichment analyses for DEGs in the top 2 modules with the highest significance were respectively conducted using the WGCNA package and the cluster Profiler package. In total, 487 upregulated and 468 downregulated DEGs were identified. A total of 24 modules were obtained from the co-expression network, and the top 2 modules with the highest significance, designated as ‘blue4’ and ‘magenta’, were further analyzed. In the module blue4, DEGs were significantly enriched in a number of Gene Ontology terms, including ‘spindle organization’ [e.g., ubiquitin conjugating enzyme E2 C (UBE2C) and SAC3 domain containing 1] and ‘cell cycle process’ [e.g., UBE2C, minichromosome maintenance complex component 6 (MCM6) and cell division cycle 20 (CDC20)]. Furthermore, a number of DEGs (e.g., UBE2C, CDC20 and MCM6) were enriched in the ‘cell cycle’ and ‘ubiquitin mediated proteolysis’ pathways. In the module ‘magenta’, a number of DEGs [e.g., transferrin receptor (TFRC) and TEA domain transcription factor 4 (TEAD4)] were enriched in the primary metabolic process and intracellular membrane-bounded organelle. Additionally, 308 upregulated genes and 215 downregulated genes were differentially expressed in the same pattern in another dataset, GSE20347, including UBE2C, CDC20, MCM6, TFRC, TEAD4, protein phosphatase 1 regulatory subunit 3C and MAL, T-cell differentiation protein. These DEGs may function in the development of ESCC.

Prognostic genes of hepatocellular carcinoma based on gene coexpression network analysis

“…In the previous study, Yin et al identified hub genes by ingenuity pathway analysis. In addition, GO and KEGG enrichment analysis were usually used to recognize hub genes . However, these analysis methods did only utilize the existed pathways and ignored the exploration of genes not included in any pathways.…”

“…In addition, GO and KEGG enrichment analysis were usually used to recognize hub genes. [10][11][12][13] However, these analysis methods did only utilize the existed pathways and ignored the exploration of genes not included in any pathways. In fact, it is possible that hub genes obtained only by bioinformatics analysis are a largely false negative.…”

Identification of Differentially Expressed Genes and miRNAs Associated with Esophageal Squamous Cell Carcinoma by Integrated Analysis of Microarray Data

“…During the past few decades, an increasing number of studies have investigated the causes and potential mechanisms of ESCC tumorigenesis. However, the high incidence and mortality of ESCC worldwide still pose a challenge, as most studies only focus on a single genetic event [9,26]. Gene profiling or microarray technologies have been widely used to predict potential targets for the treatment of different tumors.…”

“…It has been known that tumorigenesis is a complex process that involves the interaction of various genes and signaling pathways [ 26 , 27 ]. In ESCC, an increasing number of signaling pathways have been reported to play important roles in the progression of the disease [ 28 – 30 ].…”

Identification and Characterization of Copy Number-Associated Driver Genes in Esophageal Squamous Cell Carcinoma

“…Remarkably, the transcription factor LEF1 has been found to enhance beta-catenin translocation to the nucleus in ESCC [ 29 ]. TEAD4 acted as a key regulator of the functional module in ESCC by bioinformatic analysis [ 30 ]. The ligands, receptors, and TFs transported to the nucleus in the WNT signaling pathway played key roles in the tumorigenesis and progression of ESCC [ 31 , 32 ].…”