Dataset Information

Network based analyses of gene expression profile of LCN2 overexpression in esophageal squamous cell carcinoma.

ABSTRACT: LCN2 (lipocalin 2) is a member of the lipocalin family of proteins that transport small, hydrophobic ligands. LCN2 is elevated in various cancers including esophageal squamous cell carcinoma (ESCC). In this study, LCN2 was overexpressed in the EC109 ESCC cell line and we applied integrated analyses of the gene expression data to identify protein-protein interactions (PPI) network to enhance our understanding of the role of LCN2 in ESCC. Through further mining of PPI sub-networks, hundreds of differentially expressed genes (DEGs) were identified to interact with thousands of other proteins. Subcellular localization analyses found the DEGs and their directly or indirectly interacting proteins distributed in multiple layers, which was applied to analyze the possible paths between two DEGs. Gene Ontology annotation generated a functional annotation map and found hundreds of significant terms, especially those associated with the known and potential roles of LCN2 protein. The algorithm of Random Walk with Restart was applied to prioritize the DEGs and identified several cancer-related DEGs ranked closest to LCN2 protein. These analyses based on PPI network have greatly expanded our understanding of the mRNA expression profile of LCN2 overexpression for future examination of the roles and mechanisms of LCN2.

SUBMITTER: Wu B

PROVIDER: S-EPMC4066265 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Network based analyses of gene expression profile of LCN2 overexpression in esophageal squamous cell carcinoma.

Wu Bingli B Li Chunquan C Du Zepeng Z Yao Qianlan Q Wu Jianyi J Feng Li L Zhang Pixian P Li Shang S Xu Liyan L Li Enmin E

Scientific reports 20140623

LCN2 (lipocalin 2) is a member of the lipocalin family of proteins that transport small, hydrophobic ligands. LCN2 is elevated in various cancers including esophageal squamous cell carcinoma (ESCC). In this study, LCN2 was overexpressed in the EC109 ESCC cell line and we applied integrated analyses of the gene expression data to identify protein-protein interactions (PPI) network to enhance our understanding of the role of LCN2 in ESCC. Through further mining of PPI sub-networks, hundreds of dif ...[more]

PMID: 24954627

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Project description: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.

Project description:Esophageal cancer (EC) is a serious malignancy and that is the fifth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main subtype of EC in China. In recent years, long non-coding RNAs (lncRNAs) have demonstrated to be novel tumor-associated regulatory factors. However, the functions and mechanisms of lncRNAs in ESCC have not been fully understood. In this study, we attempted to construct Genome-wide expression profiles of lncRNAs and their potential functions in ESCC. By using microarray, we found a total of 2,366 lncRNAs (1,032 upregulated and 1,334 downregulated) and 3,052 mRNAs (1,477 upregulated and 1,575 downregulated) were differentially expressed between the paired five ESCC tumor tissues and adjacent normal esophageal tissues (fold change, FC ≥2.0 or ≤0.5, p ≤ 0.05). Eight lncRNAs were detected by qRT-PCR to verify the results of the microarray, and the clinicopathological parameters were analyzed in 53 patients with ESCC. GO analysis and KEGG pathway analysis showed that the main biological functions of these abnormal lncRNAs were related to immune response, extracellular vesicular exosome, and protein binding. At the same time, the cis and trans models were used to analyze the potential synergistic regulatory relationship between lncRNAs and their potential target genes. Related genes were the processes that affect cell growth, differentiation, and migration. Then we mapped the lncRNAs-mRNAs co-expression pattern by calculating the PCCs of each lncRNA and mRNA expression value. Furthermore, we investigated the function and potential mechanism of a novel highly expressed lncRNA, lnc-KIAA1244-2, and found that its expression is associated with tumor size, N classification and clinical stage. Knockdown of lnc-KIAA1244-2 inhibited the cell proliferation and inhibited the TNFAIP3 expression in Eca-109 cells. Taken together, the expression patterns of lncRNAs and mRNAs in ESCC tumor tissues are different from those in normal adjacent tissues, and some abnormal expressed lncRNAs may play important roles in the development and progression of ESCC. Lnc-KIAA1244-2 could promote the cell proliferation of ESCC cells and might be a potent therapeutic target for ESCC.

Dataset Information

Network based analyses of gene expression profile of LCN2 overexpression in esophageal squamous cell carcinoma.

Publications

Network based analyses of gene expression profile of LCN2 overexpression in esophageal squamous cell carcinoma.

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