Identification of the key transcription factors in esophageal squamous cell carcinoma

Zhang, Yuefeng; Xu, Yong; Li, Zhenhua; Zhu, Yao; Su, Wen Pang; Wang, Ming-Bo; Lv, Huilai; Zhang, Fan; Tian, Ziqiang

doi:10.21037/jtd.2017.12.27

Cited by 29 publications

(24 citation statements)

References 28 publications

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“…Recent studies have indicated that SOX10 regulates EMT in cancer [33,34]. This finding was further supported in our GSEA of GEO databases using HALLMARK gene collection (Fig.…”

Section: Resultssupporting

confidence: 86%

Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma

et al. 2019

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Background Epithelial-mesenchymal transition (EMT) is critical for cancer cell metastasis. Recently, EMT was reported to be associated with the inflammatory tumour microenvironment and, therefore, might be a predictive biomarker for immune checkpoint blockade agents. However, the underlying mechanism is still unclear. Methods Patient survival data for our HCC cohort, TCGA and GEO datasets were determined by Kaplan-Meier analysis. The functional roles of ELMO1 in HCC were demonstrated by a series of in vitro and in vivo experiments. Gene microarray analysis was used to demonstrate potential mechanisms of ELMO1. Data retrieved from the TCGA datasets were used to determine the relationships of ELMO1, EMT and TMB. Findings Here, we report an indispensable role for ELMO1 in linking EMT with tumour mutation burden (TMB), which is a promising biomarker for the immune checkpoint blockade agent response. Upregulated ELMO1 expression is associated with a poor prognosis in hepatocellular carcinoma (HCC), as well as increased cell growth, invasion, migration, angiogenesis and EMT in vitro and in vivo. Mechanistically, we provide evidence that ELMO1 regulates SOX10 expression and induces EMT through PI3K/Akt signalling. Moreover, ELMO1 is negatively associated with TMB, indicating a negative relationship between EMT and TMB. Interpretation ELMO1 serves as a link between EMT and TMB, providing a mechanistic basis for the further development of ELMO1 as a therapeutic target against HCC and potentially a promising biomarker of the immune checkpoint blockade agent response. Fund National Natural Science Foundation of China; Natural Science Foundation of Guangdong Province; Young Teacher Training Program of Sun Yat-sen University; Science and Technology Plan of Guangdong Province; Special Support Program of Guangdong Province, Science and Technology Innovation Youth Talent Support Program; the Pearl River Science and Technology New Talent of Guangzhou City; Medical Scientific Research Foundation of Guangdong Province.

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“…Recent studies have indicated that SOX10 regulates EMT in cancer [33,34]. This finding was further supported in our GSEA of GEO databases using HALLMARK gene collection (Fig.…”

Section: Resultssupporting

confidence: 86%

Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma

et al. 2019

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“…Recently, studies have found that the expression of certain genes, such as MCT4, ZNF750, Gli1, etc. was highly related to the occurrence and development of ESCC, and they might be applied as ideal biomarkers for ESCC (Cheng et al, 2018; Nambara et al, 2017; Yang et al, 2017; Zhang et al, 2018b). In addition, the aberrant expression of a few collagen family genes has also been reported to be significantly associated with the prognosis of ESCC patients.…”

Section: Discussionmentioning

confidence: 99%

The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma

Xiao

Zheng

et al. 2019

PeerJ

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Background Esophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers. Methods Clinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC. Results A total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc. Conclusion Several collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.

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“…BUB1B is also expressed at a high level in lung adenocarcinoma, and the overexpression of BUB1B is associated with poor disease progression and poor survival rates in patients with lung adenocarcinoma (37). Certain transcription factors can regulate ESCC cancer cell cycle by regulating BUB1B, which is a cell cycle-related DEG, thereby promoting the development of ESCC (38). Therefore, BUB1B may promote the development of ESCC by deregulating the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Integrative genomics analysis of hub genes and their relationship with prognosis and signaling pathways in esophageal squamous cell carcinoma

et al. 2019

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The main purpose of the present study was to recognize the integrative genomics analysis of hub genes and their relationship with prognosis and signaling pathways in esophageal squamous cell carcinoma (ESCC). The mRNA gene expression profile data of GSE38129 were downloaded from the Gene Expression Omnibus database, which included 30 ESCC and 30 normal tissue samples. The differentially expressed genes (DEGs) between ESCC and normal samples were identified using the GEO2R tool. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify the functions and related pathways of the genes. The protein-protein interaction (PPI) network of these DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes and visualized with a molecular complex detection plug-in via Cytoscape. The top five important modules were selected from the PPI network. A total of 928 DEGs, including ephrin-A1 (EFNA1), collagen type IV α1 (COL4A1), C-X-C chemokine receptor 2 (CXCR2), adrenoreceptor β2 (ADRB2), P2RY14, BUB1B, cyclin A2 (CCNA2), checkpoint kinase 1 (CHEK1), TTK, pituitary tumor transforming gene 1 (PTTG1) and COL5A1, including 498 upregulated genes, were mainly enriched in the ‘cell cycle’, ‘DNA replication’ and ‘mitotic nuclear division’, whereas 430 downregulated genes were enriched in ‘oxidation-reduction process’, ‘xenobiotic metabolic process’ and ‘cell-cell adhesion’. The KEGG analysis revealed that ‘ECM-receptor interaction’, ‘cell cycle’ and ‘p53 signaling pathway’ were the most relevant pathways. According to the degree of connectivity and adjusted P-value, eight core genes were selected, among which those with the highest correlation were CHEK1, BUB1B, PTTG1, COL4A1 and CXCR2. Gene Expression Profiling Interactive Analysis in The Cancer Genome Atlas database for overall survival (OS) was applied among these genes and revealed that EFNA1 and COL4A1 were significantly associated with a short OS in 182 patients. Immunohistochemical results revealed that the expression of PTTG1 in esophageal carcinoma tissues was higher than that in normal tissues. Therefore, these genes may serve as crucial predictors for the prognosis of ESCC.

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Identification of the key transcription factors in esophageal squamous cell carcinoma

Cited by 29 publications

References 28 publications

Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma

Intergrated analysis of ELMO1, serves as a link between tumour mutation burden and epithelial-mesenchymal transition in hepatocellular carcinoma

The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma

Integrative genomics analysis of hub genes and their relationship with prognosis and signaling pathways in esophageal squamous cell carcinoma

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