Dataset Information

Expression and clinical significance of c-Met in advanced esophageal squamous cell carcinoma.

ABSTRACT: BACKGROUND:c-Met, one of current potential hot targets, has been suggested as a potential tumor marker in the development of esophageal squamous cell carcinoma (ESCC). Our aim was to investigate the expression of c-Met in advanced esophageal squamous cell carcinoma in four phase II trials who had tumor tissues from archival in our center and analyze the correlations between c-Met expression and clinical features. METHODS:Ninety patients with advanced ESCC who were admitted to the phase II clinical trials in the Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute from March 2007 to March 2014 were finally eligible for present study and the corresponding tissues and clinical data were collected. The expression of c-Met in the tissue samples was detected by immunohistochemistry (IHC). c-Met overexpression was defined as???the median value of H-score. Kaplan-Meier and Cox multivariate regression were conducted to evaluate the relationship between c-Met expression and ESCC survival. RESULTS:The overexpression of c-Met is 43.3% in advanced ESCC. There was no statistical difference between c-Met expression and clinical features except sex and tumor location. Survival analysis documented that the overexpression of c-Met predicted a worse prognosis (OS: 253 d vs 422 d, P?=?0.011). In the group treated with chemotherapy combined with anti-EGFR drugs, patients with lowexpression of c-Met had a better OS than those with overexpression of c-Met (OS: 577 d vs 232 d, P?=?0.007). CONCLUSIONS:c-Met may be an independent prognostic factor in advanced ESCC. The overexpression of c-Met may predict a worse efficacy of anti-EGFR therapy.

SUBMITTER: Xu Y

PROVIDER: S-EPMC4307685 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Expression and clinical significance of c-Met in advanced esophageal squamous cell carcinoma.

Xu Yingying Y Peng Zhi Z Li Zhongwu Z Lu Ming M Gao Jing J Li Yilin Y Li Yanyan Y Shen Lin L

BMC cancer 20150115

<h4>Background</h4>c-Met, one of current potential hot targets, has been suggested as a potential tumor marker in the development of esophageal squamous cell carcinoma (ESCC). Our aim was to investigate the expression of c-Met in advanced esophageal squamous cell carcinoma in four phase II trials who had tumor tissues from archival in our center and analyze the correlations between c-Met expression and clinical features.<h4>Methods</h4>Ninety patients with advanced ESCC who were admitted to the ...[more]

PMID: 25588551

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Project description:BackgroundEsophageal 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.MethodsClinical 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.ResultsA 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.ConclusionSeveral 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.

Project description:The present authors previously identified a novel candidate tumor suppressor gene, zinc finger protein 750 (ZNF750), in esophageal squamous cell carcinoma (ESCC) (1). The present study aimed to clarify the clinical significance of ZNF750 expression in ESCC. The association between ZNF750 DNA mutation status and the mRNA expression was examined by whole exome sequence analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR). The expression of ZNF750 in 76 patients with ESCC (Kyushu University Beppu Hospital) was measured using immunohistochemistry and RT-qPCR. Using this dataset, the association between ZNF750 mRNA expression and clinicopathological factors was examined. Additionally, survival analysis was performed using datasets from the Kyushu University Beppu Hospital and The Cancer Genome Atlas (TCGA). The biological effects of ZNF750 expression were explored using gene set enrichment analysis (GSEA) and were validated using datasets from the Cancer Cell Line Encyclopedia (CCLE) and the Kyushu University Beppu Hospital. ZNF750 expression analyses demonstrated that ZNF750 mRNA expression was lower in patients with the DNA mutations compared with those without the mutations (P<0.05), and ZNF750 expression was downregulated in tumor tissues compared with normal tissues (P<0.00005). In the clinicopathological analysis, the low ZNF750 expression group exhibited a higher incidence of undifferentiated histology (P<0.05) compared with the high expression group. The low ZNF750 expression group exhibited a poorer prognosis in the Kyushu and TCGA datasets (P<0.0005 and P<0.05, respectively). GSEA indicated that ZNF750 expression was significantly correlated with epithelial differentiation in ESCC. This was confirmed using the datasets from CCLE and the Kyushu University Beppu Hospital by analyzing the levels of small proline rich protein 1A mRNA, an epithelial differentiation-associated gene. In conclusion, the results of the present study suggested that ZNF750 serves a role as a tumor suppressor; potentially via regulating epithelial differentiation and that it may be a promising biomarker of poor outcomes in ESCC.

Dataset Information

Expression and clinical significance of c-Met in advanced esophageal squamous cell carcinoma.

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Expression and clinical significance of c-Met in advanced esophageal squamous cell carcinoma.

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