Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population

Sawada, Genta; Niida, Atsushi; Uchi, Ryutaro; Hirata, Hidenari; Shimamura, Teppei; Suzuki, Yutaka; Shiraishi, Yuichi; Chiba, Kenichi; Imoto, Seiya; Takahashi, Yusuke; Iwaya, Takeshi; Sudo, Tomoya; Hayashi, Tomoatsu; Takai, Hiroki; Kawasaki, Yuki; Matsukawa, Takashi; Eguchi, Hidetoshi; Sugimachi, Keizō; Tanaka, Fumiaki; Suzuki, Hiromichi; Yamamoto, Ken; Ishii, Hideshi; Shimizu, Makiko; Yamazaki, Hiroshi; Yamazaki, Makoto; Tachimori, Yuji; Kajiyama, Yoshiaki; Natsugoe, Shoji; Fujita, Hiromasa; Mafune, Ken–ichi; Tanaka, Yoïchi; Kelsell, David P.; Scott, Claire A.; Tsuji, Shoji; Yachida, Shinichi; Shibata, Tatsuhiro; Sugano, Sumio; Doki, Yuichiro; Akiyama, Tetsu; Aburatani, Hiroyuki; Ogawa, Seishi; Miyano, Satoru; Mori, Masaki; Mimori, Koshi

doi:10.1053/j.gastro.2016.01.035

Cited by 277 publications

(356 citation statements)

References 43 publications

Supporting

Mentioning

314

Contrasting

Order By: Relevance

“…Additionally, 87.5% of mutations in ZNF750 led to decreased mRNA expression (1). Similarly, Lin et al (10) and Zhang et al (11) also revealed inactivating mutations (70.0 and 64.0% of mutations in each study, respectively) in ZNF750 by WES analysis of ESCC and demonstrated that the depletion of ZNF750 in ESCC cell lines promoted proliferation and invasiveness.…”

Section: Introductionmentioning

confidence: 65%

“…ZNF750 mutation. ZNF750 mutation status data were obtained from WES analysis that the authors of the present study previously performed (1). RNA from 28 patients of the 144 used in the previous study was available for quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis.…”

Section: Escc Patients and Sample Collectionmentioning

confidence: 99%

“…However, previous cohorts used to investigate the genomic abnormalities of ESCC were too small to encompass the full range of genomic abnormalities (3,4). The present authors have recently performed whole-exome sequence (WES) analysis on 144 Japanese patients with ESCC, and identified a previously uncharacterized mutant gene, zinc finger protein 750 (ZNF750) (1), which is an essential regulator of epithelial proliferation and differentiation (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinical significance of ZNF750 gene expression, a novel tumor suppressor gene, in esophageal squamous cell carcinoma

et al. 2017

Self Cite

View full text Add to dashboard Cite

Abstract. 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.

show abstract

Section: Introductionmentioning

confidence: 65%

Section: Escc Patients and Sample Collectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical significance of ZNF750 gene expression, a novel tumor suppressor gene, in esophageal squamous cell carcinoma

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Esophageal cancer has two major histological types; esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) (Napier et al 2014). ESCC is the predominant type in eastern African and Asian countries including Japan (Matsuda et al 2014); incidence of esophageal cancer among Japanese population could be resulted from synergistic effect of genetic, food and preference factors including alcohol and smoking (Sakata et al 2005;Sawada et al 2016).…”

Section: Introductionmentioning

confidence: 99%

ABCB1 Is Upregulated in Acquisition of Taxane Resistance: Lessons from Esophageal Squamous Cell Carcinoma Cell Lines

Wang

Sumarpo

Saiki

et al. 2016

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Esophageal cancer is one of the common malignancies worldwide, particularly in eastern African and Asian countries including Japan. Taxane (paclitaxel or docetaxel) is one of the effective chemotherapeutic reagents for patients with esophageal cancer, but acquisition of chemoresistance frequently occurs; this is one of the most frequent causes for therapeutic failure. In this study, we established three taxane resistant esophageal squamous cell carcinoma cell lines and explored possible mechanisms for the acquisition of chemoresistance. Microarray analyses indicated that the ABCB1 (ATP binding cassette subfamily B member 1) gene was significantly upregulated in taxane resistant esophageal cancer cell lines. Moreover, we found that siRNA mediated ABCB1 knockdown successfully restored drug sensitivity in both paclitaxel and docetaxel resistant esophageal cancer cell lines. In conclusion, we propose that ABCB1 might play a pivotal role in acquisition of taxane resistance and could be a promising target for treatment of patients with esophageal cancer after acquisition of taxane resistance.

show abstract

“…Moreover, a sequencing study including sequentially obtained samples on esophageal adenocarcinoma (EAC) revealed a majority of recurrently mutated genes in EAC to be as well present in metaplastic but never dysplastic Barrett's esophagus, while only mutations in TP53 and SMAD4 occurred stage-specific confined to high grade dysplasia and EAC (14). In addition, sequential mutational data will be interesting in correlation to clinical background such as exposition to known risk factors like abuse of alcohol and smoking as well as presence of germline polymorphisms in ALDH2 and CYP2A6 which could be linked to distinct mutational spectra in ESCC characterized by different proportions of CpG and APOBEC signatures (15). However, ESCC are usually diagnosed in an advanced stage and identification of high-risk groups for screening is difficult, especially in western countries where incidence of ESCC is markedly lower than in Asia (16,17).…”

mentioning

confidence: 99%

Intratumoral heterogeneity of esophageal squamous cell carcinoma

Walter

2017

J. Thorac. Dis.

View full text Add to dashboard Cite

Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population

Abstract: We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.

Cited by 277 publications

References 43 publications

Clinical significance of ZNF750 gene expression, a novel tumor suppressor gene, in esophageal squamous cell carcinoma

Clinical significance of ZNF750 gene expression, a novel tumor suppressor gene, in esophageal squamous cell carcinoma

ABCB1 Is Upregulated in Acquisition of Taxane Resistance: Lessons from Esophageal Squamous Cell Carcinoma Cell Lines

Intratumoral heterogeneity of esophageal squamous cell carcinoma

Contact Info

Product

Resources

About