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

Sho Nambara, Takaaki Masuda, Taro Tobo, Shinya Kidogami, Hisateru Komatsu, Keishi Sugimachi, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Koshi Mimori

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1795-1801
Number of pages7
JournalOncology Letters
Volume14
Issue number2
DOIs
Publication statusPublished - Jan 1 2017

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Zinc Fingers
Tumor Suppressor Genes
Gene Expression
Proteins
Encyclopedias
Neoplasms
Messenger RNA
Atlases
Esophageal Squamous Cell Carcinoma
Mutation
Cornified Envelope Proline-Rich Proteins
Genome
Genes
Exome
Cell Line
DNA
Survival Analysis
Reverse Transcription
Sequence Analysis
Histology

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Clinical significance of ZNF750 gene expression, a novel tumor suppressor gene, in esophageal squamous cell carcinoma. / Nambara, Sho; Masuda, Takaaki; Tobo, Taro; Kidogami, Shinya; Komatsu, Hisateru; Sugimachi, Keishi; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko; Mimori, Koshi.

In: Oncology Letters, Vol. 14, No. 2, 01.01.2017, p. 1795-1801.

Research output: Contribution to journalArticle

Nambara, Sho ; Masuda, Takaaki ; Tobo, Taro ; Kidogami, Shinya ; Komatsu, Hisateru ; Sugimachi, Keishi ; Saeki, Hiroshi ; Oki, Eiji ; Maehara, Yoshihiko ; Mimori, Koshi. / Clinical significance of ZNF750 gene expression, a novel tumor suppressor gene, in esophageal squamous cell carcinoma. In: Oncology Letters. 2017 ; Vol. 14, No. 2. pp. 1795-1801.
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AU - Sugimachi, Keishi

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