Global Gene Expression Profiling and Validation in Esophageal Squamous Cell Carcinoma and Its Association with Clinical Phenotypes

Su, Hua; Hu, Nan; Yang, Howard H.; Wang, Chaoyu; Takikita, Mikiko; Wang, Quanhong; Giffen, Carol; Clifford, Robert; Hewitt, Stephen M.; Shou, Jianzhong; Goldstein, Alisa M.; Lee, Maxwell P.; Taylor, Philip R.

doi:10.1158/1078-0432.ccr-10-2724

Cited by 212 publications

(178 citation statements)

References 32 publications

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“…Microarray gene expression and survival data of cohorts of patients with ESCC (14), esophageal adenocarcinoma (EAC; ref. 15,16), colon cancer (17,18), hepatocellular carcinoma (HCC; ref.…”

Section: Analysis Of Gene Expression and Survival Data From Cancer Pamentioning

confidence: 99%

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Guan

et al. 2016

Clinical Cancer Research

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Purpose: Chemoresistance is a major obstacle in cancer therapy. We found that fluorouracil (5-FU)-resistant esophageal squamous cell carcinoma cell lines, established through exposure to increasing concentrations of 5-FU, showed upregulation of Id1, IGF2, and E2F1. We hypothesized that these genes may play an important role in cancer chemoresistance.Experimental Design: In vitro and in vivo functional assays were performed to study the effects of Id1-E2F1-IGF2 signaling in chemoresistance. Quantitative real-time PCR, Western blotting, immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays were used to investigate the molecular mechanisms by which Id1 regulates E2F1 and by which E2F1 regulates IGF2. Clinical specimens, tumor tissue microarray, and Gene Expression Omnibus datasets were used to analyze the correlations between gene expressions and the relationships between expression profiles and patient survival outcomes.Results: Id1 conferred 5-FU chemoresistance through E2F1-dependent induction of thymidylate synthase expression in esophageal cancer cells and tumor xenografts. Mechanistically, Id1 protects E2F1 protein from degradation and increases its expression by binding competitively to Cdc20, whereas E2F1 mediates Id1-induced upregulation of IGF2 by binding directly to the IGF2 promoter and activating its transcription. The expression level of E2F1 was positively correlated with that of Id1 and IGF2 in human cancers. More importantly, concurrent high expression of Id1 and IGF2 was associated with unfavorable patient survival in multiple cancer types.Conclusions: Our findings define an intricate E2F1-dependent mechanism by which Id1 increases thymidylate synthase and IGF2 expressions to promote cancer chemoresistance. The Id1-E2F1-IGF2 regulatory axis has important implications for cancer prognosis and treatment. Clin Cancer Res; 22(5); 1243-55. Ó2015 AACR.

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“…Microarray gene expression and survival data of cohorts of patients with ESCC (14), esophageal adenocarcinoma (EAC; ref. 15,16), colon cancer (17,18), hepatocellular carcinoma (HCC; ref.…”

Section: Analysis Of Gene Expression and Survival Data From Cancer Pamentioning

confidence: 99%

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Guan

et al. 2016

Clinical Cancer Research

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“…Expression profiling of GSE11341 (Su et al, 2011) was obtained from the public functional genomics data repository Gene Expression Omnibus (GEO, http://www.ncbi.nlm. nih.gov/geo/), which is based on the Affymetrix GPL571 platform data (Affymetrix Human Genome U133A 2.0 Array).…”

Section: Expression Data Preprocessing On Pulmonary Hypoxic Diseasementioning

confidence: 99%

Expression profiling analysis of hypoxic pulmonary disease

Zhou

Wang²,

Song³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Exposure of humans to low levels of environmental oxygen results in alveolar hypoxia and normally causes chronic pulmonary hypertension and morphological alterations of precapillary pulmonary vessels. In this study, the microarray dataset GSE11341 was used to identify potential differentially expressed genes related with human lung microvascular endothelial cell hypoxia. In addition, gene ontology term enrichment analysis was performed to explore their underlying functions. In addition, we also investigated the small molecules by comparing with the Connectivity Map. We found that hypoxia samples of 3, 24, and 48 h relative to 0 h displayed 22, 21, and 29 differentially expressed genes, respectively. Among them, six genes (ADM, HMOX1, VEGFA, EGLN3, APOLD1, and ANGPTL4) were closely related to pulmonary microvascular endothelial cell hypoxia response. Three drugs (pindolol, sulfapyridine, and ciclopirox) were selected as candidates to treat hypoxia-related pulmonary diseases. In conclusion, our results provide some underlying drug targets for treatment of hypoxic pulmonary patients.

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“…Because of its prevalence, recent genetic and genomic studies have focused on understanding esophageal squamous cell carcinoma (ESCC) in Chinese populations (1,2). In this type of cancer, oxidative damage occurs continuously in DNA as a result of normal metabolism as well as other internal and external factors.…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of the DNA repair enzyme MYH in esophageal squamous cell carcinoma

Shen

Chen

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. MYH is an important enzyme in combating DNA oxidative stress in the occurrence and development of various types of tumors. To investigate the correlation between expression of the DNA repair enzyme MYH in esophageal squamous cell carcinoma and 8-oxoguanine (8-oxoG) oxidative damage, as well as the clinical significance of altered MYH expression, tissues from 175 esophageal carcinoma cases were investigated in the present study. MYH expression and 8-oxoG oxidative damage in squamous cell carcinoma and adjacent normal tissue were assessed by immunohistochemistry and Western blotting. In 82.9% (145/175) of the cases, MYH protein expression in esophageal squamous cell carcinoma was lower than that of adjacent normal tissue (t=4.24, P<0.001). Additionally, 8-oxoG staining was higher in the tumors than in the normal tissue. Lower expression of MYH in esophageal squamous cell carcinoma was associated with depth of invasion, venous invasion, TNM stage and lymph node metastasis (P<0.05). In conclusion, a lower MYH expression level in esophageal cell carcinoma tissue was inversely associated with more severe 8-oxoG oxidative damage, suggesting that changes in MYH activity correspond to increased DNA damage in tumor cells. The use of MYH expression as a postoperative index for esophageal squamous cell carcinoma may guide the formulation of individualized chemotherapy for patients after surgery.

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Global Gene Expression Profiling and Validation in Esophageal Squamous Cell Carcinoma and Its Association with Clinical Phenotypes

Cited by 212 publications

References 32 publications

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Expression profiling analysis of hypoxic pulmonary disease

Expression and clinical significance of the DNA repair enzyme MYH in esophageal squamous cell carcinoma

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